Amitriptyline for Prolonged Cutaneous Analgesia in the Rat

Background: Amitriptyline has been reported to be a more potent local anesthetic than bupivacaine. In keeping with the objective of identifying drugs for prolonged cutaneous analgesia, the authors compared the cutaneous analgesic effectiveness of amitriptyline and bupivacaine in rats.

Methods: Rats were subcutaneously injected on shaved dorsal skin. The skin wheal raised after injection of 0.6 ml of various concentrations of either amitriptyline or bupivacaine with and without epinephrine (1:200,000) was marked. Inhibition of the cutaneous trunci muscle reflex was evaluated quantitatively by the fraction of times a total of six pinpricks applied to the marked area failed to elicit a nocifensive motor response compared with control responses. No responses out of six pinpricks was defined as 100% maximum possible effect.

Results: Complete recovery from the cutaneous analgesia elicited by 0.05% and 0.5 amitriptyline versus 0.05 and 0.5% bupivacaine occurred in 9.9 +/- 0.2 and 19.3 +/- 0.4 h versus 2.2 +/- 0.1 and 16.1 +/- 0.2 h, respectively (mean +/- SE). Addition of epinephrine increased this duration to 14.1 +/- 0.1 and 21.4 +/- 0.2 h versus 3.2 +/- 0.1 and 17.0 +/- 0.3 h, respectively. Complete nociceptive blockade after coinjection of 0.25% amitriptyline, 0.25% bupivacaine, and epinephrine lasted 24 +/- 0.5 h, and com-plete recovery from this block took 33 +/- 0.5 h. Areas under the percent maximum possible effect versus time curve were 1,770 +/- 24 and 1,471 +/- 50% h for 0.5% amitriptyline and bupivacaine with epinephrine, respectively, whereas this value was 2,836 +/- 62% h for the coinjected 0.25% amitriptyline, 0.25% bupivacaine, and epinephrine admixture.     

Amitriptyline versus bupivacaine in rat sciatic nerve blockade

BACKGROUND: Amitriptyline, a tricyclic antidepressant, is frequently used orally for the management of chronic pain. To date there is no report of amitriptyline producing peripheral nerve blockade. The authors therefore investigated the local anesthetic properties of amitriptyline in rats and in vitro. METHODS: Sciatic nerve blockade was performed with 0.2 ml amitriptyline or bupivacaine at selected concentrations, and the motor, proprioceptive, and nociceptive blockade was evaluated. Cultured rat GH3 cells were externally perfused with amitriptyline or bupivacaine, and the drug affinity toward inactivated and resting Na+ channels was assessed under whole-cell voltage clamp conditions. In addition, use-dependent blockade of these drugs at 5 Hz was evaluated. RESULTS: Complete sciatic nerve blockade for nociception was obtained with amitriptyline for 217 +/- 19 min (5 mM, n = 8, mean +/- SEM) and for 454 +/- 38 min (10 mM, n = 7) versus bupivacaine for 90 +/- 13 min (15.4 mM, n = 6). The time to full recovery of nociception for amitriptyline was 353 +/- 12 min (5 mM) and 656 +/- 27 min (10 mM) versus 155 +/- 9 min for bupivacaine (15.4 mM). Amitriptyline was approximately 4.7-10.6 times more potent than bupivacaine in binding to the resting channels (50% inhibitory concentration [IC50] of 39.8 +/- 2.7 vs. 189.6 +/- 22.3 microM) at - 150 mV, and to the inactivated Na+ channels (IC50 of 0.9 +/- 0.1 vs. 9.6 +/- 0.9 microM) at -60 mV. High-frequency stimulation at 3 microM caused an additional approximately 14% blockade for bupivacaine, but approximately 50% for amitriptyline. CONCLUSION: Amitriptyline is a more potent blocker of neuronal Na+ channels than bupivacaine in vivo and in vitro. These findings suggest that amitriptyline could extend its clinical usefulness for peripheral nerve blockade.     

Amitriptyline versus Bupivacaine in Rat Sciatic Nerve Blockade

Background: Amitriptyline, a tricyclic antidepressant, is frequently used orally for the management of chronic pain. To date there is no report of amitriptyline producing peripheral nerve blockade. The authors therefore investigated the local anesthetic properties of amitriptyline in rats and in vitro.

Methods: Sciatic nerve blockade was performed with 0.2 ml amitriptyline or bupivacaine at selected concentrations, and the motor, proprioceptive, and nociceptive blockade was evaluated. Cultured rat GH3 cells were externally perfused with amitriptyline or bupivacaine, and the drug affinity toward inactivated and resting Na+ channels was assessed under whole-cell voltage clamp conditions. In addition, use-dependent blockade of these drugs at 5 Hz was evaluated.

Results: Complete sciatic nerve blockade for nociception was obtained with amitriptyline for 217 +/- 19 min (5 mm, n = 8, mean +/- SEM) and for 454 +/- 38 min (10 mm, n = 7) versus bupivacaine for 90 +/- 13 min (15.4 mm, n = 6). The time to full recovery of nociception for amitriptyline was 353 +/- 12 min (5 mm) and 656 +/- 27 min (10 mm) versus 155 +/- 9 min for bupivacaine (15.4 mm). Amitriptyline was approximately 4.7-10.6 times more potent than bupivacaine in binding to the resting channels (50% inhibitory concentration [IC50] of 39.8 +/- 2.7 vs. 189.6 +/- 22.3 [mu]m) at -150 mV, and to the inactivated Na+ channels (IC50 of 0.9 +/- 0.1 vs. 9.6 +/- 0.9 [mu]m) at -60 mV. High-frequency stimulation at 3 [mu]m caused an additional approximately 14% blockade for bupivacaine, but approximately 50% for amitriptyline.     

Epinephrine enhances analgesia produced by epidural bupivacaine during labor

Reports on the analgesic and hemodynamic effects of epinephrine added to bupivacaine for epidural use in obstetrics are conflicting. In this study, healthy parturients received in a random manner either 10 ml of 0.25% bupivacaine (n = 50) or 10 ml of 0.25% bupivacaine with 1:300,000 epinephrine (n = 50) epidurally. Epinephrine enhanced the analgesia produced by bupivacaine: onset was hastened (5.8 +/- 0.6 vs 8.7 +/- 0.8 min, mean +/- SEM, P less than 0.05), duration prolonged (123 +/- 7.0 vs 92 +/- 5.0 min, P less than 0.05), and the number of women requiring additional local anesthetic for analgesia decreased (9 vs 18, P less than 0.05) compared to the group receiving plain bupivacaine. The incidence of hypotension did not differ between groups. Maternal heart rate increased only after injection of the epinephrine-containing solution. The authors conclude that epinephrine 1:300,000 modestly but statistically significantly improves the analgesic efficacy of epidurally administered 0.25% bupivacaine during labor.     

Isobolographic analysis of epinephrine with bupivacaine, dextromethorphan, 3-methoxymorphinan, or dextrorphan on infiltrative anesthesia in rats: dose-response studies

BACKGROUND AND OBJECTIVES: The aims of this study were to establish the potencies of epinephrine, bupivacaine, dextromethorphan, 3-methoxymorphinan, and dextrorphan and evaluate interactions of epinephrine with bupivacaine, dextromethorphan, 3-methoxymorphinan, or dextrorphan as an infiltrative anesthetic. Bupivacaine, a common and long-acting local anesthetic, was used as control. METHODS: Dose-dependent responses of epinephrine, dextromethorphan, 3-methoxymorphinan, and dextrorphan on cutaneous analgesia were compared with bupivacaine in rats. The interactions of drugs were evaluated via an isobolographic analysis. RESULTS: We found that epinephrine, bupivacaine, dextromethorphan, 3-methoxymorphinan, and dextrorphan produced a dose-dependent local anesthetic effect as infiltrative cutaneous analgesia. Relative potencies were epinephrine > bupivacaine > dextromethorphan > 3-methoxymorphinan > dextrorphan (P < .01 for each comparison). Coadministration of bupivacaine with epinephrine produced a synergistic effect, and coadministration of dextromethorphan, 3-methoxymorphinan, or dextrorphan with epinephrine produced an additive effect. CONCLUSIONS: Epinephrine, dextromethorphan, 3-methoxymorphinan, and dextrorphan are known to have local anesthetic effects as infiltrative cutaneous analgesia in rats. Epinephrine increased the potency of bupivacaine, but not dextromethorphan, 3-methoxymorphinan, or dextrorphan as an infiltrative anesthetic. The cutaneous analgesic effects of adding epinephrine to dextromethorphan, 3-methoxymorphinan, or dextrorphan, are similar to combinations of 2 local anesthetics.     

Preincisional treatment to prevent pain after ambulatory hernia surgery

We designed this study as a randomized comparison of postoperative pain after inguinal hernia repair in patients treated with triple preincisional analgesic therapy versus standard care. Triple therapy consisted of a nonsteroidal antiinflammatory, a local anesthetic field block, and an N-methyl-D-aspartate inhibitor before incision. The treatment group (n = 17) received rofecoxib, 50 mg PO, a field block with 0.25% bupivacaine/0.5% lidocaine, and ketamine 0.2 mg/kg IV before incision; controls (n = 17) received a placebo PO before surgery. The anesthetic protocol was standardized. Postoperative pain was treated by fentanyl IV and oxycodone 5 mg/acetaminophen 325 mg PO as required for pain. Pain scores (0-10) and analgesic were recorded for the first 7 days after surgery. Pain scores were 47% lower in the treatment group before discharge (3.1 +/- 0.6 versus 5.9 +/- 0.6, P = 0.0026) (mean +/- SE) and 18% less in the first 24 h after discharge (5.6 +/- 0.4 versus 6.8 +/- 0.5, P = 0.05); oral analgesic use was 34% less in the treatment group (4.6 +/- 0.8 doses versus 7.1 +/- 0.7 doses, P = 0.02) in the first 24 h after surgery. We conclude that triple preincisional therapy diminishes pain and analgesic use after outpatient hernia repair, and encourage further evaluation of this technique. IMPLICATIONS: Outpatients undergoing inguinal hernia repair under general anesthesia report moderate-to-severe pain after surgery. Triple preincisional therapy that included rofecoxib, 50 mg PO, ketamine, 0.2 mg/kg IV, and local anesthetic field block reduced pain scores and analgesic use in the first 24 h after discharge.     

Cutaneous analgesia after transdermal application of amitriptyline versus lidocaine in rats

Amitriptyline, a tricyclic antidepressant, has potent local anesthetic properties. However, there is no report of cutaneous analgesic effects after transdermal application. We report here that transdermally applied amitriptyline is more potent than lidocaine in providing cutaneous analgesia in rats. Solutions of amitriptyline base in 50, 100, and 500 mM concentrations were applied as a patch to rats, and their effects were compared with those of lidocaine base at the same concentrations and of the vehicle alone (45% water, 45% isopropyl alcohol, and 10% glycerin). Rats in each test group developed a concentration-dependent cutaneous analgesic block in the areas to which the drugs were applied; however, amitriptyline produced a longer block than lidocaine at the same concentration. The development of amitriptyline as a longer-lasting topical analgesic may improve our ability to treat chronic pain, such as neuropathic pain and neuralgia, and to prevent pain in procedures such as venipuncture. IMPLICATIONS: The tricyclic antidepressant amitriptyline, often used perorally for the management of chronic pain, is shown here to be more potent than lidocaine in providing cutaneous analgesia when applied transdermally with an occlusive dressing in rats.     

Use of a continuous local anesthetic infusion for pain management after median sternotomy

BACKGROUND: The use of large doses of opioid analgesics to treat pain after cardiac surgery can prolong the time to tracheal extubation and interfere with recovery of bowel and bladder function in the postoperative period. Therefore, the authors investigated the efficacy of a continuous infusion of bupivacaine 0.25% or 0.5%, at the median sternotomy site, for 48 h after cardiac surgery in reducing the opioid analgesic requirement and improving the recovery process. METHODS: In this prospective, randomized, placebo-controlled, double-blind clinical trial, 36 consenting patients undergoing open-heart surgery with a standardized general anesthetic technique had two indwelling infusion catheters placed at the median sternotomy incision site at the end of surgery. The patients were randomly assigned to receive normal saline (control), bupivacaine 0.25% or bupivacaine 0.5% via an elastomeric infusion pump at a constant rate of 4 ml/h for 48 h. Patients evaluated their chest pain using an 11-point verbal rating scale, with 0 = no pain to 10 = worst pain imaginable. In addition, the postoperative opioid analgesic requirements and opioid-related adverse effects were recorded. Patient satisfaction with their pain management was assessed at specific intervals during the postoperative period using a 100-point verbal rating scale, with 1 = highly dissatisfied to 100 = highly satisfied. Finally, serum bupivacaine concentrations were measured 24 and 48 h after surgery. RESULTS: Compared with the control group, there was a statistically significant reduction in verbal rating scale pain scores and patient-controlled analgesia morphine use in the bupivacaine-0.5% group. Patient satisfaction with their pain management was also improved in the bupivacaine-0.5% (vs. control) group. However, there were no significant differences in patient-controlled analgesia morphine use between the bupivacaine-0.25% and control groups. Although the duration of the intensive care unit stay (30 vs. 34 h, respectively) was not significantly decreased, the time to ambulation (1 +/- 0.5 vs. 2 +/- 1 days, respectively) and the duration of hospital stay (4.2 vs. 5.7 days, respectively) were lower in the bupivacaine-0.5% group than in the control group. Mean +/- SD serum bupivacaine concentrations at 48 h in the bupivacaine-0.25% and bupivacaine-0.5% groups were 0.5 +/- 0.5 and 1.3 +/- 0.7 microg/ml, respectively. CONCLUSION: A continuous infusion of bupivacaine 0.5% at 4 ml/h is effective for decreasing pain and the need for opioid analgesic medication as well as for improving patient satisfaction with their pain management after cardiac surgery. Patients in the bupivacaine-0.5% group were able to ambulate earlier, leading to a reduced length of hospital stay.     

Clonidine combined with a long acting local anesthetic does not prolong postoperative analgesia after brachial plexus block but does induce hemodynamic changes

Clonidine in brachial plexus block prolongs analgesia of local anesthetics of short and intermediate duration. We performed a prospective randomized double-blinded study to determine the efficacy and adverse effects of clonidine mixed with a long-acting local anesthetic on postoperative analgesia. Sixty adult patients underwent elective rotator cuff repair using interscalene brachial plexus block combined with general anesthesia and were randomly divided into one of the following three groups. Placebo (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine (1/200000) and 1 mL of 0.9% saline, completed by 1 mL of 0.9% saline IM in the controlateral shoulder; Control (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine and 1 mL of 0. 9% saline, completed by 150 microg (=1 mL) of clonidine IM; Clonidine (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine and 150 microg (=1 mL) of clonidine, completed by 1 mL of 0.9% saline IM. During anesthesia hemodynamic variables and fractional expired isoflurane concentration (FeISO) were recorded. The following postoperative variables were assessed: duration of interscalene block, quality of pain relief on a visual analog scale, side effects, and consumption of morphine with a patient-controlled analgesia device over 48 h. Patient characteristics were comparable. During anesthesia mean arterial pressure, heart rate, and FeISO were significantly decreased in Clonidine and Control groups compared with Placebo group. Duration of analgesia, defined as the time elapsed from interscalene injection to the first morphine request, was 983 +/- 489 min in the Placebo, 909 +/- 160 min in the Control, and 829 +/- 159 min in the Clonidine groups. Pain scores and consumption of morphine at 24 h and 48 h showed no differences among the three groups. We conclude that adding 150 microg of clonidine in interscalene block does not prolong analgesia induced by 40 mL of bupivacaine 0.5% with epinephrine, but decreases mean arterial blood pressure and heart rate. Implications: Clonidine in brachial plexus block does not improve postoperative analgesia when mixed with a long-lasting anesthetic. Nevertheless, with or without clonidine, bupivacaine in interscalene block provides a long-lasting analgesia of approximately 15 h.     

Use of a Continuous Local Anesthetic Infusion for Pain Management after Median Sternotomy

Background: The use of large doses of opioid analgesics to treat pain after cardiac surgery can prolong the time to tracheal extubation and interfere with recovery of bowel and bladder function in the postoperative period. Therefore, the authors investigated the efficacy of a continuous infusion of bupivacaine 0.25% or 0.5%, at the median sternotomy site, for 48 h after cardiac surgery in reducing the opioid analgesic requirement and improving the recovery process.

Methods: In this prospective, randomized, placebo-controlled, double-blind clinical trial, 36 consenting patients undergoing open-heart surgery with a standardized general anesthetic technique had two indwelling infusion catheters placed at the median sternotomy incision site at the end of surgery. The patients were randomly assigned to receive normal saline (control), bupivacaine 0.25% or bupivacaine 0.5%via an elastomeric infusion pump at a constant rate of 4 ml/h for 48 h. Patients evaluated their chest pain using an 11-point verbal rating scale, with 0 = no pain to 10 = worst pain imaginable. In addition, the postoperative opioid analgesic requirements and opioid-related adverse effects were recorded. Patient satisfaction with their pain management was assessed at specific intervals during the postoperative period using a 100-point verbal rating scale, with 1 = highly dissatisfied to 100 = highly satisfied. Finally, serum bupivacaine concentrations were measured 24 and 48 h after surgery.

Results: Compared with the control group, there was a statistically significant reduction in verbal rating scale pain scores and patient-controlled analgesia morphine use in the bupivacaine-0.5% group. Patient satisfaction with their pain management was also improved in the bupivacaine-0.5% (vs. control) group. However, there were no significant differences in patient-controlled analgesia morphine use between the bupivacaine-0.25% and control groups. Although the duration of the intensive care unit stay (30 vs. 34 h, respectively) was not significantly decreased, the time to ambulation (1 +/- 0.5 vs. 2 +/- 1 days, respectively) and the duration of hospital stay (4.2 vs. 5.7 days, respectively) were lower in the bupivacaine-0.5% group than in the control group. Mean +/- SD serum bupivacaine concentrations at 48 h in the bupivacaine-0.25% and bupivacaine-0.5% groups were 0.5 +/- 0.5 and 1.3 +/- 0.7 [mu]g/ml, respectively.     

Use of a charged lidocaine derivative, tonicaine, for prolonged infiltration anesthesia

BACKGROUND AND OBJECTIVES: We tested the hypothesis that the duration of cutaneous anesthesia elicited by the permanently charged compound N-phenylethyl lidocaine (tonicaine) would be longer than that elicited by its parent structure, lidocaine, and that it would be less affected by epinephrine (epi), after subcutaneous injection in rats, as a model for infiltration anesthesia. METHODS: Subcutaneous injections were performed on the shaved dorsal skin of rats with either tonicaine or lidocaine (0.1% or 0.5%, n = 8 in each group) with and without epi (1:200,000). Inhibition of the cutaneous trunci muscle reflex was quantitatively evaluated by a blinded observer by the number of times pinpricks failed to elicit the nocifensive motor response out of a total of 6 pinpricks applied to the injected area. RESULTS: Duration of complete nociceptive blockade in the 0.5% tonicaine and lidocaine groups was 619 +/- 47 and 58 +/- 2 minutes, respectively; duration of full recovery in these groups was 1,106 +/- 19 and 86 +/- 3 minutes, respectively. Epi increased the duration of complete block in the 0.5% tonicaine and lidocaine groups to 750 +/- 13 and 97 +/- 11 minutes, respectively, and the duration of full recovery to 1,185 +/- 13 and 172 +/- 6 minutes, respectively. Skin toxicity was seen only in the 0.5% tonicaine with epi group (3 of 8 rats). CONCLUSIONS: Tonicaine is a substantially longer lasting local anesthetic with a delayed onset of action compared with lidocaine and may be useful in situations where long duration of infiltration block is desirable.     

The Dose-Response of Caudal Ropivacaine in Children

Background: Ropivacaine, a new local anesthetic, is less cardiotoxic in adults and is less likely to cause motor blockade than is bupivacaine. The authors evaluated the clinical effectiveness and hemodynamic effects of ropivacaine compared with bupivacaine and the pharmacokinetics of ropivacaine when given for caudal blocks in 56 children 4.1 +/- 1.2 yr old (mean +/- SD).

Methods: Patients scheduled for inguinal hernia repair were randomly given a caudal injection (0.75 ml/kg) of ropivacaine, 0.25% (R0.25 group); ropivacaine, 0.5% (R0.5 group); or bupivacaine, 0.25% (B0.25 group). Postoperative measurements included the duration of analgesia, which was our primary outcome variable, and hemodynamic and respiratory monitoring for 4 h in the recovery room. Thereafter, analgesic requirements for the following 24 h were assessed by an independent observer on the ward using an observational pain-discomfort scale, which gives a cumulative score from 5 to 15 to estimate the quality of analgesia by assessment of behavioral objective parameters. Plasma levels of ropivacaine were measured before the procedure was started and 5, 10, 15, 20, 25, 30, and 45 min and 1, 2, 4, 6, 8, and 24 h after caudal block.

Results: A significantly longer (P < 0.0001) duration of analgesia (median [range]) was observed in the R0.5 group (1,440 [335-1,440] min), whereas the R0.25 group (208 [175-340] min) and the B0.25 group (220 [100-390] min) were comparable. All groups showed a significant decrease in mean arterial blood pressure and heart rate from baseline values, but differences between groups were not observed.     

A multicenter,randomized, controlled trial comparing bupivacaine with ropivacaine for labor analgesia

BACKGROUND: A meta-analysis of studies comparing high doses of bupivacaine with ropivacaine for labor pain found a higher incidence of forceps deliveries, motor block, and poorer neonatal outcome with bupivacaine. The purpose of this study was to determine if there is a difference in these outcomes when a low concentration of patient-controlled epidural bupivacaine combined with fentanyl is compared with ropivacaine combined with fentanyl. METHODS: This was a multicenter, randomized, controlled trial, including term, nulliparous women undergoing induction of labor. For the initiation of analgesia, patients were randomized to receive either 15 ml bupivacaine, 0.1%, or 15 ml ropivacaine, 0.1%, each with 5 microg/ml fentanyl. Analgesia was maintained with patient-controlled analgesia with either local anesthetic, 0.08%, with 2 microg/ml fentanyl. The primary outcome was the incidence of operative delivery. We also examined other obstetric, neonatal, and analgesic outcomes. RESULTS: There was no difference in the incidence of operative delivery between the two groups (148 of 276 bupivacaine recipients vs. 135 of 279 ropivacaine recipients; P = 0.25) or any obstetric or neonatal outcome. The incidence of motor block was significantly increased in the bupivacaine group compared with the ropivacaine group at 6 h (47 of 93 vs. 29 of 93, respectively; P = 0.006) and 10 h (29 of 47 vs. 16 of 41, respectively; P = 0.03) after injection. Satisfaction with mobility was higher with ropivacaine than with bupivacaine (mean +/- SD: 76 +/- 23 vs. 72 +/- 23, respectively; P = 0.013). Satisfaction for analgesia at delivery was higher for bupivacaine than for ropivacaine (mean +/- SD: 71 +/- 25 vs. 66 +/- 26, respectively; P = 0.037). CONCLUSIONS: There was no difference in the incidence of operative delivery or neonatal outcome among nulliparous patients who received low concentrations of bupivacaine or ropivacaine for labor analgesia.     

Comparison of 40 milliliters of 0.25% intrapleural bupivacaine with epinephrine with 20 milliliters of 0.5% intrapleural bupivacaine with epinephrine after cholecystectomy

To determine the influence of the volume of local anesthetic injected for intrapleural analgesia, 40 patients undergoing cholecystectomy were randomly allocated to two groups of 20 patients each. One group received 40 mL of 0.25% bupivacaine with epinephrine injected intrapleurally postoperatively. The other group received 20 mL of 0.5% bupivacaine with epinephrine. The onset time of analgesia was nearly the same in both groups and within 25 min all patients were nearly pain free. Our data demonstrate that 100 mg of bupivacaine with epinephrine elicits effective analgesia after cholecystectomy. There are only minor differences between 20 and 40 mL with regard to pain relief. The authors conclude that the volume of local anesthetic within the range of 20-40 mL in an adult has little influence on the extent or duration of intrapleural analgesia.     

Does a preemptive block of the great auricular nerve improve postoperative analgesia in children undergoing tympanomastoid surgery?

We performed a double-blinded randomized controlled trial to evaluate the efficacy of preemptive analgesia in children undergoing tympanomastoid surgery. Children were divided into two groups: group block-block (BB) received a preemptive great auricular nerve block (GAN-block) with 0.25% bupivacaine with 1:200,000 epinephrine before incision followed by a second GAN-block with 0.25% bupivacaine with 1:200,000 epinephrine 1 h before the end of the procedure. Group sham block-block (SB-B) received a preemptive GAN-block with normal saline before surgical incision followed by a GAN-block with 0.25% bupivacaine with 1:200000 epinephrine 1 h before the completion of the procedure. All patients were evaluated for pain with the objective pain score (OPS) by a blinded observer. There was no difference in pain rescue requirements in the postanesthesia care unit (BB versus SB-B, 1 of 20 versus 3 of 20, P= 0.60) or in the short-stay unit (BB versus SB-B, 5 of 20 versus 11 of 20, P = 0.107) or for the entire hospital stay (P = 0.20). There was no significant difference between groups in the time to first rescue pain medication (BB versus SB-B, 226 +/- 71 min versus 201 +/- 94 min). There was no significant difference between groups regarding vomiting in the postoperative period (P = 0.52). We conclude that a preoperative GAN-block does not offer significant advantages for postoperative pain relief in children undergoing tympanomastoid surgery. IMPLICATIONS: This double-blinded randomized controlled trial compared the efficacy of preemptive analgesia with a peripheral nerve block of the great auricular nerve for decreasing postoperative pain in children undergoing tympanomastoid surgery. Preemptive analgesia did not improve the quality or duration of postoperative analgesia in our cohort.     

A comparison of 0.1% and 0.2% ropivacaine and bupivacaine combined with morphine for postoperative patient-controlled epidural analgesia after major abdominal surgery

Ropivacaine (ROPI), which is less toxic and produces less motor block than bupivacaine (BUPI), seems attractive for epidural analgesia. Few data are available concerning dose requirements of epidural ROPI when combined with morphine. In this study, we compared the dose requirements and side effects of ROPI and BUPI combined with small-dose morphine after major abdominal surgery. Postoperatively, 60 patients were randomly allocated (double-blinded manner) to four groups: patient-controlled epidural analgesia with the same settings using 0.1% or 0.2% solution of ROPI or BUPI combined with an epidural infusion of 0.1 mg/h of morphine. Pain scores, side effects, motor block, and local anesthetic consumption were measured for 60 h. Pain scores and the incidence of side effects did not differ among the groups. Consumption of ROPI and BUPI were similar in both 0.1% groups. Doubling the concentration significantly reduced the consumption (milliliters) of BUPI (P < 0.05) but not of ROPI. Consequently, using ROPI 0.2% significantly increased the dose administered as compared with ROPI 0.1% (ROPI 0.1% = 314 +/- 151 mg and ROPI 0.2% = 573 +/- 304 mg at Hour 48; P < 0.05). Patient-controlled epidural analgesia with the 0.1% or 0.2% solution of ROPI or BUPI combined with epidural morphine resulted in comparable analgesia. As compared with ROPI 0.1%, the use of ROPI 0.2% increased consumption of local anesthetic without improving analgesia. IMPLICATIONS: Small-dose (0.1%) ropivacaine and bupivacaine have similar potency and result in comparable analgesia and incidence of side effects.     

The dose-response of caudal ropivacaine in children.

BACKGROUND: Ropivacaine, a new local anesthetic, is less cardiotoxic in adults and is less likely to cause motor blockade than is bupivacaine. The authors evaluated the clinical effectiveness and hemodynamic effects of ropivacaine compared with bupivacaine and the pharmacokinetics of ropivacaine when given for caudal blocks in 56 children 4.1 +/- 1.2 yr old (mean +/- SD). METHODS: Patients scheduled for inguinal hernia repair were randomly given a caudal injection (0.75 ml/kg) of ropivacaine, 0.25% (R0.25 group); ropivacaine, 0.5% (R0.5 group); or bupivacaine, 0.25% (B0.25 group). Postoperative measurements included the duration of analgesia, which was our primary outcome variable, and hemodynamic and respiratory monitoring for 4 h in the recovery room. Thereafter, analgesic requirements for the following 24 h were assessed by an independent observer on the ward using an observational pain-discomfort scale, which gives a cumulative score from 5 to 15 to estimate the quality of analgesia by assessment of behavioral objective parameters. Plasma levels of ropivacaine were measured before the procedure was started and 5, 10, 15, 20, 25, 30, and 45 min and 1, 2, 4, 6, 8, and 24 h after caudal block. RESULTS: A significantly longer (P < 0.0001) duration of analgesia (median [range]) was observed in the R0.5 group (1,440 [335-1,440] min), whereas the R0.25 group (208 [175-340] min) and the B0.25 group (220 [100-390] min) were comparable. All groups showed a significant decrease in mean arterial blood pressure and heart rate from baseline values, but differences between groups were not observed. CONCLUSION: Ropivacaine is well tolerated and provides effective analgesia when given for caudal blockade in small children for inguinal hernia repair.     

Epinephrine does not prolong the analgesia of 20 mL ropivacaine 0.5% or 0.2% in a femoral three-in-one block.

We tested the effect of epinephrine added to 20 mL ropivacaine 0.5% and 0.2% on postoperative analgesia via a femoral catheter after total knee replacement. Forty-one patients undergoing total knee replacement under combined peripheral block/general anesthesia were randomly allocated to two groups. After insertion of a femoral catheter, 21 patients in the Ropivacaine-Epinephrine (ROPI-EPI) group received 20 mL ropivacaine 0.5% plus epinephrine 1:200,000, whereas 20 patients in the Ropivacaine group (ROPI) received 20 mL plain ropivacaine 0.5%. Thereafter, a sciatic block with 30 mL bupivacaine 0.5% plus epinephrine 1:200,000 was performed in all patients, followed by general anesthesia. After surgery, patient-controlled analgesia (PCA) with ropivacaine 0.2% plus epinephrine 1:200,000 for Group ROPI-EPI and plain ropivacaine 0.2% for Group ROPI was available via the femoral catheter (200 mL ropivacaine 0.2% +/- epinephrine, bolus 20 mL, lockout 120 min). The patients were instructed to use PCA when the knee pain score was >3 cm. The interval between the initial ropivacaine injection and the first PCA injection determined the duration of 20 mL ropivacaine 0.5% +/- epinephrine, whereas the interval between the first and second PCA injection determined the duration of 20 mL ropivacaine 0.2% +/- epinephrine. The average duration of ropivacaine 0.5% was 657 +/- 345 min for the ROPI-EPI group and 718 +/- 423 min for the ROPI group (NS), whereas for ropivacaine 0.2%, the average duration was 409 +/- 245 min for the ROPI-EPI group and 419 +/- 339 min for the ROPI group (not significant). We conclude that epinephrine does not influence the duration of analgesia of the ropivacaine concentrations investigated. IMPLICATIONS: We evaluated the effect of epinephrine on the duration of analgesia of 20 mL ropivacaine 0.5% or 0.2% injected in femoral three-in-one block for pain relief after total knee replacement. Our results show that epinephrine does not alter the duration of analgesia of the two solutions investigated.     

The dose-sparing effect of clonidine added to ropivacaine for labor epidural analgesia

To determine the effects of clonidine with ropivacaine during epidural labor analgesia, we studied 66 nulliparous women in early active labor. Women were randomized to receive ropivacaine 0.1% 8 mL plus 75 microg of clonidine (Group 1), ropivacaine 0.2% 8 mL plus 0.5 mL of NaCl 0.9% (Group 2), or ropivacaine 0.2% 8 mL plus 75 microg of clonidine (Group 3) 5 min after a bupivacaine 7.5 mg with epinephrine 15 microg test dose. Upon request, additional analgesia with ropivacaine 0.1% 8 mL followed by ropivacaine 0.2% 8 mL/h was administered. With clonidine, duration of analgesia was increased (132 +/- 48 min [Group 1] and 154 +/- 42 min [Group 3] versus 91 +/- 44 min [Group 2]; P < 0.05), and total ropivacaine dose over the first 4 h was significantly reduced (40.5 +/- 15 mg [Group 1] and 47.0 +/- 16 mg [Group 3] versus 72.5 +/- 18 mg [Group 2]; P < 0.01). The incidence of more profound motor block was more frequent in Group 2 (P < 0.05). Although there was a trend for more women receiving clonidine to require ephedrine for treatment of hypotension, this did not seem to have an impact on fetal outcome or incidence of cesarean deliveries for nonreassuring fetal heart rate tracings. This study demonstrates the dose-sparing effect of clonidine when added to ropivacaine. IMPLICATIONS: The effect of adding 75 microg of clonidine to ropivacaine for epidural labor analgesia was studied. Clonidine increased analgesia duration and produced dose sparing compared with ropivacaine alone. Despite a tendency for hypotension in women receiving clonidine, there was no apparent effect on delivery mode or neonatal outcome.     

Continuous interpleural infusion of bupivacaine for postoperative analgesia after surgery with flank incisions: a double-blind comparison of 0.25% and 0.5% solutions.

Postoperative analgesia, as assessed by visual analogue scale scores (0-10) and patient-controlled analgesia morphine requirements, pulmonary function (forced vital capacity and forced expiratory volume in 1 s), and plasma bupivacaine concentrations were studied in patients receiving interpleural blockade with bupivacaine after surgery with a flank incision. Two groups of 10 patients received either 0.5% or 0.25% bupivacaine, both with epinephrine (5 micrograms/mL). Pain relief was initiated when patients had visual analogue scale scores greater than or equal to 4. Patients received 21 mL of bupivacaine 0.25% or 0.5% in a double-blind fashion. One hour later, a continuous infusion of 5 mL/h of the study solution was started. At the same time, patient-controlled analgesia became accessible to the patients. The onset time of pain relief and the area under the visual analogue scale score-time curves over the first 8 h were similar in both groups. Patient-controlled analgesia morphine use was also similar in the 0.25% (21.3 +/- 14.6 mg) and 0.5% (21.0 +/- 16.0 mg) groups (mean +/- SD). In both groups, forced vital capacity and forced expiratory volume in 1 s improved significantly within 60 min (P less than 0.05). Peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC) over 24 h were higher (P less than 0.001) in the 0.5% group (Cmax, 1.47 +/- 0.37 micrograms/mL; AUC, 1511 +/- 323 micrograms.mL-1.min) than those in the 0.25% group (Cmax, 0.55 +/- 0.22 micrograms/mL; AUC, 680 +/- 118 micrograms.mL-1.min) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)