Peter G. Atanassoff

Ziconotide, a new n-type calcium channel blocker, administered intrathecally for acute postoperative pain

Background and Objectives: Voltage‐sensitive calcium channel conductance is essential for the nervous system to signal a painful event. However, intrathecal administration of L‐type calcium channel blockers does not provide analgesia. The present investigation was designed to assess the safety and analgesic efficacy of ziconotide, a new N‐type calcium channel blocker, when administered intrathecally to patients with acute postoperative pain. Methods: This randomized, double‐blind, pilot study included patients undergoing elective total abdominal hysterectomy, radical prostatectomy, or total hip replacement. After intrathecal injection of local anesthetic and before surgical incision, a continuous intrathecal infusion of either placebo or 1 of 2 doses of ziconotide (0.7 μg/h or 7.0 μg/h) was started and continued for 48 to 72 hours postoperatively. Primary and secondary efficacy variables were the mean daily patient controlled analgesia (PCA) morphine equivalent consumption and visual analog pain intensity (VASPI) scores, respectively. Results: Thirty patients received study drug; 26 were evaluable for efficacy. Mean daily PCA morphine equivalent consumption was less in patients receiving ziconotide than in placebo‐treated patients, and the difference was statistically significant between 24 and 48 hours (P = .040). VASPI scores during the first 8 hours postoperatively were markedly lower in ziconotide‐treated than in placebo‐treated patients. In 4 of 6 patients receiving the high‐dose of ziconotide (7 μg/h), adverse events, such as dizziness, blurred vision, nystagmus, and sedation contributed to study drug being discontinued after 24 hours. After ziconotide discontinuation, these symptoms resolved. Conclusions: Ziconotide showed analgesic activity, as shown by decreased PCA morphine equivalent consumption and lower VASPI scores. Because of a favorable trend of decreased morphine consumption with an acceptable side‐effect profile in the low‐dose ziconotide group, 0.7 μg/h may be closer to the ideal dose than 7 μg/h. Large‐scale studies are required to clarify this issue.

Attenuation of experimental pruritus and mechanically evoked dysesthesiae in an area of cutaneous allodynia.

We investigated the effects of tactile allodynia on the itch and mechanically evoked dysesthesiae produced by an intradermal injection of histamine in human volunteers. After an intradermal injection of capsaicin into the volar surface of one forearm, there developed an area of tactile allodynia to stroking and hyperalgesia to pricking the skin. Histamine was then injected simultaneously into the area of allodynia (experimental arm) and into the opposite forearm (control arm). Magnitude estimates of itch were obtained every 15 s for 5 min, and the areas of cutaneous hyperalgesia (pricking-evoked pain), alloknesis (stroking-evoked itch), hyperknesis (pricking-evoked itch) and wheal and flare were measured. The areas of wheal and flare were not significantly different on the two arms. The magnitude of itch and the areas of hyperknesis and alloknesis developed normally on the control arm but were absent or greatly reduced on the experimental arm. Thus, both the itch and the alloknesis and hyperknesis normally induced by histamine were absent or greatly reduced when histamine was injected in an area of capsaicin-induced allodynia. These results are compatible with the hypothesis that activity in capsaicin-sensitive, nociceptive primary afferent neurons evokes a central neuronal inhibitory process that prevents or reduces the itch and mechanically evoked dysesthesiae normally produced by an intradermal injection of histamine.

Electromyographic Comparison of Obturator Nerve Block to Three-in-one Block

Obturator nerve block during spinal, epidural, or general anesthesia without muscle relaxants has been recommended for transurethral surgery to prevent thigh adductor muscle contractions during operative electrocautery.We investigated the effectiveness of direct obturator and 3-in-1 nerve motor blocks in 44 patients undergoing transurethral surgery during spinal anesthesia with isobaric bupivacaine. Patients were randomly assigned to receive 3-in-1 block with 40 mL (n = 13) or 50 mL (n = 11) of 1.5% lidocaine plus epinephrine, or direct obturator nerve block with 10 mL of 2% lidocaine plus epinephrine (n = 20). After both direct obturator and 3-in-1 blocks, compound muscle action potential (CMAP) testing of the obturator nerve was performed at 1-10-s intervals for 10 min. In patients given direct obturator nerve block (n = 20), CMAP amplitude decreased by 88.8 +/- 21% (mean +/- SD) from baseline. In contrast, 3-in-1 block reduced the evoked CMAP amplitude by 7.4 +/- 19% (P < 0.05). Peak lidocaine plasma levels of 1.6 +/- 0.2 micro gram/mL (range 1.0-2.8 micro gram/mL) were reached 60-90 min after the block in those patients receiving 50 mL of local anesthetic. The 3-in-1 technique fails to predictably result in effective motor block of the obturator nerve and thus may not prevent inadvertent thigh adductor muscle contractions during transurethral surgery. A direct approach to the obturator nerve is significantly more effective in producing motor block, and even when given in larger than recommended dosages it results in subtoxic peak plasma lidocaine concentrations. (Anesth Analg 1995;81:529-33)

Ropivacaine 0.2% and lidocaine 0.5% for Intravenous regional anesthesia in outpatient surgery

BackgroundA longer-acting local anesthetic agent, such as ropivacaine, may offer advantages over lidocaine for intravenous regional anesthesia. The objectives of this study were to evaluate whether the findings of volunteer investigations with intravenous regional anesthesia with ropivacaine (which have shown prolonged analgesia after release of the tourniquet) translates into improved pain control after surgery. MethodsWith Human Investigation Committee approval and a double-blind study design, 20 healthy patients with American Society of Anesthesiologists physical status I or II classification who were scheduled to undergo forearm and hand surgery were randomly assigned to administration of 40 ml of either 0.2% ropivacaine or 0.5% lidocaine for intravenous regional anesthesia. Evidence of central nervous system side effects, such as lightheadedness, tinnitus, and metallic taste, as well as cardiac arrhythmias, were evaluated and treated (if necessary) after local anesthetic administration, before and during surgery, and after release of the tourniquet until discharge from the postanesthesia care unit. Regression of sensory anesthesia in the nerve distributions of the forearm and hand was recorded. Verbal numerical pain scores were monitored and quantified until the patients were discharged to home from the postanesthesia care unit. Patient pain scores, side effect profiles, time to first oral intake, and total amount of oral analgesics were recorded 24 h postoperatively. ResultsIntravenous regional anesthesia with 0.2% ropivacaine and 0.5% lidocaine provided equivalent levels of surgical anesthesia. After release of the tourniquet, the first evidence for return of sensation in the distribution of the five peripheral nerves occurred later in the ropivacaine group (median, 20 min; range, 15–40 min) than in the lidocaine group (median, 1 min; range, 1–25 min). Verbal numerical pain scores were significantly lower at the time of admission, whereas during the remainder of the postanesthesia care unit stay and later at home, the difference in verbal numerical pain scores between the two groups was no longer statistically significant. ConclusionsRopivacaine 0.2% may be an alternative to 0.5% lidocaine for intravenous regional anesthesia in the outpatient surgical setting. Longer-lasting analgesia in the immediate postoperative period may be due to a more profound and prolonged tissue binding effect of ropivacaine.

What is the minimum effective volume of local anesthetic required for sciatic nerve blockade? A prospective, randomized comparison between a popliteal and a subgluteal approach

For sciatic nerve blockade, no study has defined the optimal volume of local anesthetic required to block the nerve. The current, prospective, randomized investigation was designed to find a minimum volume of 1.5% mepivacaine required to block the sciatic nerve using the subgluteal and posterior popliteal approaches. A total of 56 patients undergoing foot surgery were randomly assigned to receive sciatic nerve block by means of a posterior subgluteal (group subgluteal, n = 28) or a posterior popliteal (group popliteal, n = 28) approaches. All blocks were performed with the use a nerve stimulator (stimulating frequency, 2 Hz, intensity 1.5-0.5 mA) and a perineural stimulating catheter. In all patients, plantar flexion of the foot was elicited at <0.5 mA, to maintain consistency among groups. The volume of local anesthetic used in each patient was based on the modified Dixon’s up-and-down method. Complete anesthesia was defined as complete loss of pinprick sensation in the sciatic nerve distribution with concomitant inability to perform plantar or dorsal flexion of the foot 20 min after injection. The mean volume of local anesthetic required to block the sciatic nerve was 12 ± 3 mL in the subgluteal group and 20 ± 3 mL in the popliteal group (P < 0.05). The ED95 for adequate block of the sciatic nerve was 17 mL in the subgluteal group and 30 mL in the popliteal group. The authors conclude that a larger volume of local anesthetic is necessary to block the sciatic nerve at a more distal site (popliteal approach) as compared with a more proximal level (subgluteal approach).

Plantar flexion seems more reliable than dorsiflexion with Labat's sciatic nerve block: A prospective, randomized comparison

Labat’s classic approach to the sciatic nerve has not been able to show which motor response of the foot provides a more frequent rate of complete sensory and motor block. In this prospective, randomized, double-blind study, we compared plantar flexion with dorsiflexion with regard to onset time and efficacy of sciatic nerve block using the classic posterior approach. A total of 80 patients undergoing hallux valgus repair were randomly allocated to receive sciatic nerve block after evoked plantar flexion (n = 40) or dorsiflexion (n = 40). Twenty milliliters of 0.75% ropivacaine was injected after the motor response was elicited at <0.5 mA. Success rate was defined as complete sensory and motor block in all sciatic nerve distributions associated with a pain-free surgery. Time required for onset of sensory and motor block of the foot was recorded. Success was more frequent after elicited plantar flexion (87.5%) than dorsiflexion (55%; P < 0.05). Onset of complete sensory and motor block of the foot was faster after elicited plantar flexion (10 ± 10 min and 13 ± 10 min, respectively) compared with dorsiflexion (20 ± 11 min and 24 ± 12 min; P < 0.05). We conclude that plantar flexion of the foot predicts a shorter onset time and a more frequent success rate than dorsiflexion with Labat’s classic posterior sciatic nerve block.

Intercostal Nerve Block for Lumpectomy: Superior Postoperative Pain Relief with Bupivacaine

STUDY OBJECTIVES To investigate whether equipotent doses of lidocaine and bupivacaine were equally effective for intercoastal nerve blockade (ICNB) and whether a lower amount of lidocaine would be comparably effective. To see whether plasma levels of lidocaine with and without epinephrine and of plain bupivacaine would reach toxic ranges. Finally, to evaluate the duration of postoperative analgesia following general anesthesia and regional anesthesia with two different local anesthetics. DESIGN Randomized, double-blind study, with control group administered general anesthesia. SETTING Gynecologic operating room of a university hospital. PATIENTS 48 adult ASA physical status I and II otherwise healthy patients undergoing lumpectomy. INTERVENTIONS 36 patients received ICNB of T3-T6 unilaterally using either 4 ml/segment of 1.5% lidocaine with epinephrine 3.75 micrograms/ml (n = 10, Group A), 4 ml/segment of 2% lidocaine with epinephrine 5 micrograms/ml (n = 13, Group B), or 4 ml/segment of plain 0.5% bupivacaine (n = 13, Group C). The control group consisted of 12 patients (Group D) who received a general anesthetic using propofol, alfentanil, and nitrous oxide in oxygen for induction and maintenance of anesthesia. MEASUREMENTS AND MAIN RESULTS In all three ICNB groups, the highest plasma concentrations were reached after 5 to 10 minutes following ICNB--i.e., a lidocaine plasma level of 2.77 +/- 0.5 micrograms/ml (mean +/- SEM) in Group A, a lidocaine plasma level of 2.78 +/- 0.2 micrograms/ml in Group B, and a bupivacaine plasma level of 1.44 +/- 0.2 micrograms/ml in Group C. There were no significant differences in plasma levels between 1.5% lidocaine and 2% lidocaine. For the first 90 minutes after surgery, higher postoperative pain scores were found in the control group than in the ICNB groups. Notably longer-lasting postoperative pain relief was achieved with plain bupivacaine. The number of women requiring postoperative analgesic medication, the time of first request, and the total amount of analgesic drugs administered during the 24 hours postoperatively were significantly lower in the regional anesthesia groups than in the general anesthesia group (p < 0.05). CONCLUSIONS ICNB is an alternative to general anesthesia for female breast surgery. Both lidocaine with epinephrine and plain bupivacaine in the doses used did not raise venous plasma concentrations to levels considered potentially toxic. With respect to duration of postoperative pain relief and analgesic drug request, the local anesthetics (in particular, bupivacaine) were found to be superior to general anesthesia.

Is ultrasound guidance superior to conventional nerve stimulation for coracoid infraclavicular brachial plexus block

Background and Objectives: In different peripheral nerve blocks, it has been speculated that needle guidance by ultrasound improves onset time and success rate compared with the more frequently used nerve stimulation-guided technique. In the present study, we tested the hypothesis that ultrasound guidance improves onset time of coracoid infraclavicular brachial plexus block (IBPB) when compared with a nerve stimulation-guided technique. Methods: Seventy patients scheduled for hand or forearm surgery were randomly assigned to receive coracoid IBPB using either ultrasound guidance (group U, n = 35), or nerve stimulation (group S, n = 35). Patients were assessed for sensory and motor block every 5 mins after injection of local anesthetic. Onset time, the primary end point, was defined as the time required for complete sensory and motor block. Time required to perform the block, success rate, and time to resolution of motor blockade were also recorded (secondary end points). Results: Onset of complete sensory and motor blockade was similar in the 2 groups (17 mins [8 mins] in group U and 19 mins [8 mins] in group S; P = 0.321). Time required to perform the block was shorter in group U (3 mins [1 min]) as compared with group S (6 mins [2 mins]; P < 0.0001). No differences were observed in success rate (89% in group U and 91% in group S; P = 0.881) and time to resolution of motor blockade (237 mins [45 mins] in group U and 247 mins [57 mins] in group S; P = 0.418). Conclusions: The present investigation demonstrates that ultrasound guidance and nerve stimulation provide similar onset time, success rate, and duration of motor blockade for coracoid IBPB; however, ultrasound guidance reduces the time required to perform the block.

Comparison of Continuous Infusion versus Automated Bolus for Postoperative Patient-controlled Analgesia with Popliteal Sciatic Nerve Catheters

Background:This investigation was designed to compare a new methodology of automated regular bolus with a continuous infusion of local anesthetic for continuous popliteal sciatic block; both regimens were combined with patient-controlled analgesia (PCA). Methods:Fifty patients undergoing hallux valgus repair were randomly allocated to receive an infusion of 0.125% levobupivacaine administered through a popliteal catheter as an automated regular bolus (n = 25) or as a continuous infusion (n = 25), both combined with PCA. Postoperative pain scores, incremental doses delivered by the PCA, local anesthetic consumed per hour, and the need for rescue tramadol analgesia were recorded. Results:Both dosing regimens provided similar postoperative analgesia. Consumption of local anesthetic (5.14 ml/h, 5–5.75 ml/h) and dose request from the PCA (1, 0–5.4) was lower in the automated bolus group as compared to the continuous infusion group (5.9 ml/h, 5.05–7.8 ml/h; doses by PCA: 6.5, 0–20.5; P < 0.05). The need for rescue tramadol was similar in the two groups. Conclusion:In continuous popliteal sciatic block, local anesthetic administered as an automated regular bolus in conjunction with PCA provided similar pain relief as a continuous infusion technique combined with PCA; however, the new dosing regimen reduced the need for additional PCA and the overall consumption of local anesthetic.

Comparison of ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in volunteers.

UNLABELLED A longer acting local anesthetic such as ropivacaine may offer advantages over lidocaine for IV regional anesthesia (IVRA). The objective of this investigation was to determine whether the use of ropivacaine improves the quality and duration of IVRA. In a randomized, double cross-over design, 10 volunteers received lidocaine 0.5% or ropivacaine 0.2% for IVRA of the upper extremity on two separate days with a standard double-cuff technique. Sensation to pinprick, response to tetanic stimuli, and tourniquet pain were assessed on a 0-10 verbal numeric score scale at 5-min intervals throughout the period of tourniquet inflation. Motor function was evaluated by grip strength. After release of the second (distal) cuff, pinprick sensation, motor strength, and systemic side effects were evaluated at 3, 10, and 30 min. No significant differences were observed for onset times of anesthesia and times to proximal (38 +/- 3 and 36 +/- 3 min) or distal (34 +/- 13 and 36 +/- 13 min) tourniquet release after the administration of ropivacaine and lidocaine, respectively. However, postdeflation hypoalgesia and motor blockade were prolonged with ropivacaine, and postdeflation light-headedness, tinnitus, and drowsiness were more prominent with lidocaine. We conclude that ropivacaine may be an alternative to lidocaine for IVRA. It may result in prolonged analgesia and fewer side effects after tourniquet release. IMPLICATIONS In this study, volunteers received lidocaine 0.5% or ropivacaine 0.2% for IV regional anesthesia on two study days. Ropivacaine and lidocaine provided similar surgical conditions. However, after release of the distal tourniquet, prolonged sensory blockade and fewer central nervous system side effects were observed with ropivacaine.