Table 2. Clinical findings for most extensively studied agents not covered by recent meta-analyses.
| Agent | Local Anesthetic | Site/Dose | Prolongation of Analgesia or Sensory Block | Side Effects & Toxicity | Systemic Control (route) | Jadad Scale (I-V) |
|---|---|---|---|---|---|---|
| Buprenorphine | Bupivacaine 0.5% + epi[18] | Sciatic—0.3mg | 6h* | PONV events: 7 in control group, 21 in IM buprenorphine group, 19 in PN buprenorphine group | No | V |
| Buprenorphine | Mepivacaine 1% + tetracaine 0.02% + epi[16] | Axillary—0.3mg | 15h** | None | No | III+ |
| Buprenorphine | Mepivacaine 1% + tetracaine 0.02% + epi[17] | SCB—0.3mg | 12h? | PONV in 2/20 in PN buprenorphine group, 6/20 in IM buprenorphine group, and 3/20 in control group | Yes | V |
| Buprenorphine | Levobupivacaine 0.75%[19] | ISB—0.15mg | 6h*** | PONV in 4/50 pts; hypotension in 1/50 pts | No | IV+ |
| Buprenorphine | Lidocaine 1% + bupivacaine 0.5%[15] | SCB- 3mcg/kg | 9h* | Pruritus in 4/20 pts; PONV in 10/20 pts | No | II |
| Buprenorphine | Bupivacaine 0.3%[20] | SCB- 3mcg/kg | 6h** | PONV in 2/20 pts in PN buprenorphine group and 2/20 pts in IM buprenorphine group. No buprenorphine-free control group. | Yes (IM) | III |
| Morphine | Bupivacaine 0.5% + epi[25] | ISB- 5mg | None | 1) PONV in 5/20 pts in placebo group and 10/20 pts in morphine group. Pruritus in 3/20 in placebo group and 0/20 in morphine group. | No | III |
| Morphine | Bupivacaine 0.5%[26] | Intercostal- 4mg | None | None | No | III |
| Morphine | Lidocaine 1.5% + epi[24] | Axillary—0.1mg/kg | None (Note: decreased opiate consumption) | Pruritus in 1/20 PN morphine; nausea in 1/20 PN morphine and 2/20 IV morphine. No morphine-free control group. | Yes (IV) | III |
| Morphine | Lidocaine 1% + bupivacaine 0.5%[15] | SCB- 75mcg/kg | 10h* | Pruritus in 1/20 pts. PONV in 2/20 in morphine group, 1/20 in control group | No | II |
| Morphine | Lidocaine 1% + bupivacaine 0.5%[27] | Axillary- 4mg | None | PONV in 2/19 PN morphine and 4/21 IV morphine. No morphine-free control group. | Yes (IM) | III |
| Morphine | Bupivacaine 0.125%[28] | Popliteal- 10mg | 3h* | Somnolence and nausea in 14/46 pts in morphine phase and 0/46 pts during bupivacaine-alone phase. Decreased BP and HR described in morphine phase without data. | No | IV |
| Fentanyl | Ropivacaine 0.75%[30] | Axillary- 20mcg | None | Not reported | No | V |
| Fentanyl | Lidocaine 1.5% + epi[29] | Axillary- 100mcg | None | Not reported | No | V |
| Fentanyl | Lidocaine 1.5% + epi[31] | Axillary- 100mcg | 1h**,*** | Not reported | Yes (IV) | V |
| Fentanyl | Ropivacaine 0.75%[33] | Sciatic/femoral- 1mcg/kg | None | No difference in sedation or oxygen saturation | No | IV+ |
| Fentanyl | Mepivacaine 1.5% + epi[32] | SCB- 75mcg | 1h** | Not reported | Yes (IM) | III |
| Fentanyl | Lidocaine 1.5%[34] | ISB- 75mcg | None | Not reported | No | V |
| Fentanyl | Bupivacaine 0.25%[35] | Axillary- 100mcg | 3h***, 10h** | Nausea in 1/20 pts in each fentanyl group, 0/20 in control group. No sedation in any group. | No | III+ |
| Fentanyl | Articaine 2%[36] | Axillary- 100mcg | 2h*, 1h*** | 5/22 with sedation in fentanyl group, 2/22 with sedation in control group | No | V |
| Fentanyl | Bupivacaine 0.25% + épi[37] | Paravertebral—0.6mcg/kg | 12h* | None | No | V |
| Fentanyl | Bupivacaine 0.5% + lidocaine 2%[38] | Cervical plexus- 50mcg | 3h* | Bradycardia in 2/38 in fentanyl group, 1/39 in control group. Hypercapnia in 3/38 in fentanyl group, 1/38 in control group. | No | V |
| Epinephrine | Lidocaine 1.5%[42] | Axillary- 200mcg/ml | 45min** | Tachycardia and hypertension with 200mcg | No | IV |
| Epinephrine | Mepivacaine 1%[43] | Brachial plexus- 200mcg | 1h*** | None | No | III+ |
| Epinephrine | Ropivacaine 0.5% and 0.2%[44] | Femoral- 5mcg/ml | None* | None | No | IV |
| Clonidine | Bupivacaine 0.375%[53] | Sciatic popliteal- 100mcg | ~3-4h** | None | Yes (IM) | V |
| Clonidine | Levobupivacaine 0.5%[54] | Sciatic popliteal- 150mcg | None* | 50% with clonidine experience. >20% decrease in systolic BP | No | V |
| Clonidine | Ropivacaine 0.5%[55] | Axillary- 150mcg | None*** | None | No | IV+ |
| Clonidine | Bupivacaine 0.5%[56] | SCB- 1mcg/kg vs. 2mcg/kg | 21h with 2mcg/kg, 15h with 1mcg/kg | Higher hypotension, bradycardia, and sedation in 2mcg/kg group | No | V |
| Clonidine | Bupivacaine 0.5%[57] | SCB- 30mcg | 220min* | Sedation | No | V |
| Clonidine | Lidocaine 1.5% (note: comparison to epinephrine 5mcg/ml)[58] | Cervical plexus- 5mcg/ml | None** | Increased lidocaine plasma concentrations compared to epinephrine | No | V |
| Clonidine | Bupivacaine 0.5% and lidocaine 2% (note: comparison to 5mg midazolam)[59] | SCB- 150mcg | None** | None | No | I+ |
| Dexmedetomidine | Bupivacaine 0.375%[64] | SCB- 100mcg | ~8h* | Bradycardia in one patient | No | III+ |
| Dexmedetomidine | Ropivacaine 0.5%[65] | ISB- 150mcg | ~4h** | Lower HR with dexmedetomidine, no neurotoxicity | No | V |
| Dexmedetomidine | Ropivacaine 0.375%[66] | Cervical plexus- 1mcg/kg | ~50min** | Sedation, bradycardia requiring atropine | No | III+ |
| Dexmedetomidine | Mepivacaine 1%[43] | Brachial plexus- 1mcg/kg | ~75min** | Bradycardia | No | III+ |
| Dexmedetomidine | Ropivacaine 0.75%[67] | Ulnar nerve block- 20mcg | ~200min*** | None | Yes (IV) | IV |
| Dexmedetomidine | Ropivacaine 0.5%[68] | Posterior tibial- 1mcg/kg | ~4.5h** | Hypotension, bradycardia | No | V |
| Dexmedetomidine | Bupivacaine 0.25%[69] | SCB- 1mcg/kg | ~180min* | Bradycardia | No | V |
| Dexamethasone | Lidocaine 1.5% + epi[73] | SCB- 8mg | 3h** | None | No | V |
| Dexamethasone | Prilocaine 2%[76] | Axillary- 8mg | 3h** | Not reported | No | IV+ |
| Dexamethasone | Bupivacaine 0.5%[77] | Sciatic/saph- 8mg; ankle- 8mg | Sciatic/saph—13% of patients with pain in first 24hrs vs. 47% in IM group; ankle—none | Not reported | Yes (IM) | V |
| Dexamethasone | Ropivacaine 0.5%[78] | ISB- 10mg | None | 3.8- and 5.1-mg/dL increase in blood glucose with PN and IV administration | Yes (IV) | V |
| Dexamethasone | Bupivacaine 0.5% + epi[79] | Sciatic- 8mg | None | Statistically insignificant increase in incidence of numbness and paresthesia at 24 and 48hrs. No symptoms persisted at 8wks in any group. | Yes (IV) | V |
| Dexamethasone | Bupivacaine 0.25%[74] | TAP- 8mg | 1h* | Decreased nausea and vomiting (6/30 with dexamethasone vs. 14/30 with control). | No | IV+ |
| Dexamethasone | Bupivacaine 0.25%[81] | SCB- 1mg, 2mg, 4mg | 10h* | One transient paresthesia noted in 2mg group | Yes (IV) | V |
| Tramadol | Levobupivacaine 0.5%[89] | ISB—1.5mg/kg | 7h* | None | Yes (IM) | V |
| Tramadol | Lidocaine 1.5% + epi[90] | Axillary- 200mg | 160min*, 65min*** | None | No | V |
| Tramadol | Levobupivacaine 0.5% + lidocaine 2%[91] | Axillary- 100mg | None* | Sedation, nausea | No | IV+ |
| Tramadol | Levobupivacaine 0.5%[92] | Psoas—1.5mg/kg | None* | None | Yes (IV) | V |
| Tramadol | Mepivacaine 1.5%[93] | Axillary- 40mg, 100mg, 200mg | 60min, 40min, 40min* | Nausea/vomiting | No | IV |
| Tramadol | Mepivacaine 1%[94] | Axillary- 100mg | 100min*** | None | Yes (IV) | IV |
| Tramadol | Ropivacaine 0.75%[95] | Axillary- 100mg | None* | None | No | V |
| Tramadol | Bupivacaine 0.5%[96] | Paravertebral—1.5mg/kg | None* | None | No | V |
| Magnesium | Bupivacaine 0.25%[102] | Femoral- 500mg | 10h*, 2h*** | Not reported | No | III |
| Magnesium | Bupivacaine 0.5%[103] | ISB- 200mg | 2h* | Nausea 2-3x more frequently at 4, 8, and 12hrs postoperatively with magnesium | No | V |
| Magnesium | Prilocaine 2%[104] | Axillary- 150mg, 100mg | 2h***, 1h*** | None | Yes (150mg IV) | II |
| Magnesium | Levobupivacaine 0.5%[105] | Axillary- 150mg | 150min*** | No thrombi or vasospasm in any group. Other side effects not reported. | No | III+ |
| Magnesium | Levobupivacaine 0.25%[105] | Axillary- 150mg | 100min*** | No thrombi or vasospasm in any group. Other side effects not reported. | No | III+ |
Abbreviations: SCB = supraclavicular block; ISB = interscalene block; PN = perineural; IM = intramuscular; IV = intravenous; BP = blood pressure; HR = heart rate; saph = saphenous; POD = postoperative day; SQ = subcutaneous; GI = gastrointestinal; TAP = transversus abdominis plane; epi = epinephrine; PONV = postoperative nausea and vomiting; pts: patients.
*Time to first analgesic;
**Time to first reported pain;
***Time to pinprick or restoration of sensation.