Peter S. Hodgson

The Neurotoxicity of Drugs Given Intrathecally (spinal)

Overall, most spinal drugs in clinical use have been poorly studied for spinal cord and nerve root toxicity. Laboratory studies indicate that all local anesthetics are neurotoxic in high concentrations and that lidocaine and tetracaine have neurotoxic potential in clinically used concentrations. However, spinal anesthesia (including lidocaine and tetracaine) has a long and enviable history of safety. Spinal analgesics such as morphine, fentanyl, sufentanil, clonidine, and neostigmine seem to have a low potential for neurotoxicity based on laboratory and extensive clinical use. Most antioxidants, preservatives, and excipients used in commercial formulations seem to have a low potential for neurotoxicity. In addition to summarizing current information, we hope that this review stimulates future research on spinal drugs to follow a systematic approach to determining potential neurotoxicity. Such an approach would examine histologic, physiologic, and behavioral testing in several species, followed by cautious histologic, physiologic, and clinical testing in human volunteers and patients with terminal cancer refractory to conventional therapy.

Epidural lidocaine decreases sevoflurane requirement for adequate depth of anesthesia as measured by the Bispectral Index monitor.

Background Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS). Methods After premedication with 0.02 mg/kg midazolam and 1 &mgr;g/kg fentanyl, 30 patients aged 20–65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 &mgr;g · kg−1 · min−1). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up–down methodology based on BIS less than 50 (MACBIS50). Plasma lidocaine concentrations were measured. Results The MACBIS50 of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1 %;P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 &mgr;g/ml) were similar to those in the epidural lidocaine group (2.0 &mgr;g/ml). Conclusions Epidural anesthesia reduced by 34% the sevoflurane required for adequate depth of anesthesia. This effect was not a result of systemic lidocaine absorbtion, but may have been caused by deafferentation by epidural anesthesia or direct rostral spread of local anesthetic within the cerebrospinal fluid. Lower-than-expected concentrations of volatile agents may be sufficient during combined epidural–general anesthesia.

A comparison of spinal, epidural, and general anesthesia for outpatient knee arthroscopy.

We compared general, epidural, and spinal anesthesia for outpatient knee arthroscopy (excluding anterior cruciate ligament repairs). Forty-eight patients (ASA physical status I–III) were randomized to receive either propofol-nitrous oxide general anesthesia with a laryngeal mask airway with anesthetic depth titrated to a bispectral index level of 40–60, 15–20 mL of 3% 2-chloroprocaine epidural, or 75 mg of subarachnoid procaine with 20 &mgr;g fentanyl. All patients were premedicated with <0.035 mg/kg midazolam and <1 &mgr;g/kg fentanyl and received intraarticular bupivacaine and 15–30 mg of IV ketorolac during the procedure. Recovery times, operating room turnover times, and patient satisfaction were recorded by an observer using an objective scale for recovery assessment and a verbal rating scale for satisfaction. Statistical analysis was performed with analysis of variance and &khgr;2. Postanesthesia care unit discharge times for the general and epidural groups were similar (general = 104 ± 31 min, epidural = 92 ± 18 min), whereas the spinal group had a longer recovery time (146 ± 52 min) (P = 0.0003). Patient satisfaction was equally good in all three groups (P = 0.34). Room turnover times did not differ among groups (P = 0.16). There were no anesthetic failures or serious adverse events in any group. Pruritus was more frequent in the spinal group (7 of 16 required treatment) than in the general or epidural groups (no pruritus) (P < 0.001). We conclude that epidural anesthesia with 2-chloroprocaine provides comparable recovery and discharge times to general anesthesia provided with propofol and nitrous oxide. Spinal anesthesia with procaine and fentanyl is an effective alternative and is associated with a longer discharge time and increased side effects. Implications For outpatient knee arthroscopy, anesthesia can be provided adequately with regional or general anesthesia. Epidural and general anesthesia provide equal recovery times and patient satisfaction, whereas spinal anesthesia may prolong recovery and have increased side effects. The choice of anesthesia may depend primarily on the patient’s interest in being alert or asleep during the procedure.

Does Epidural Anesthesia Have General Anesthetic Effects? A Prospective, Randomized, Double-blind, Placebo-controlled Trial

BACKGROUND Clinically, patients require surprisingly low end-tidal concentrations of volatile agents during combined epidural-general anesthesia. Neuraxial anesthesia exhibits sedative properties that may reduce requirements for general anesthesia. The authors tested whether epidural lidocaine reduces volatile anesthetic requirements as measured by the minimum alveolar concentration (MAC) of sevoflurane for noxious testing cephalad to the sensory block. METHODS In a prospective, randomized, double-blind, placebo-controlled trial, 44 patients received 300 mg epidural lidocaine (group E), epidural saline control (group C), or epidural saline-intravenous lidocaine infusion (group I) after premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl. Tracheal intubation followed standard induction with 4 mg/kg thiopental and succinylcholine 1 mg/kg. After 10 min or more of stable end-tidal sevoflurane, 10 s of 50 Hz, 60 mA tetanic electrical stimulation were applied to the fifth cervical dermatome. Predetermined end-tidal sevoflurane concentrations and the MAC for each group were determined by the up-and-down method and probit analysis based on patient movement. RESULTS MAC of sevoflurane for group E, 0.52+/-0.18% (+/- 95% confidence interval [CI]), differed significantly from group C, 1.18+/-0.18% (P < 0.0005), and from group I, 1.04+/-0.18% (P < 0.001). The plasma lidocaine levels in groups E and I were comparable (2.3+/-1.0 vs. 3.0+/-1.2 microg/ml +/- SD). CONCLUSIONS Lidocaine epidural anesthesia reduced the MAC of sevoflurane by approximately 50%. This MAC sparing is most likely caused by indirect central effects of spinal deafferentation and not to systemic effects of lidocaine or direct neural blockade. Thus, lower concentrations of volatile agents than those based on standard MAC values may be adequate during combined epidural-general anesthesia.

Dose-response effects of spinal neostigmine added to bupivacaine spinal anesthesia in volunteers.

BACKGROUND Intrathecal adjuncts often are used to enhance small-dose spinal bupivacaine for ambulatory anesthesia. Neostigmine is a novel spinal analgesic that could be a useful adjunct, but no data exist to assess the effects of neostigmine on small-dose bupivacaine spinal anesthesia. METHODS Eighteen volunteers received two bupivacaine spinal anesthetics (7.5 mg) in a randomized, double-blinded, crossover design. Dextrose, 5% (1 ml), was added to one spinal infusion and 6.25, 12.5, or 50 microg neostigmine in dextrose, 5%, was added to the other spinal. Sensory block was assessed with pinprick; by the duration of tolerance to electric stimulation equivalent to surgical incision at the pubis, knee, and ankle; and by the duration of tolerance to thigh tourniquet. Motor block at the quadriceps was assessed with surface electromyography. Side effects (nausea, vomiting, pruritus, and sedation) were noted. Hemodynamic and respiratory parameters were recorded every 5 min. Dose-response relations were assessed with analysis of variance, paired t tests, or Spearman rank correlation. RESULTS The addition of 50 microg neostigmine significantly increased the duration of sensory and motor block and the time until discharge criteria were achieved. The addition of neostigmine produced dose-dependent nausea (33-67%) and vomiting (17-50%). Neostigmine at these doses had no effect on hemodynamic or respiratory parameters. CONCLUSIONS The addition of 50 microg neostigmine prolonged the duration of sensory and motor block. However, high incidences of side effects and delayed recovery from anesthesia with the addition of 6.25 to 50 microg neostigmine may limit the clinical use of these doses for outpatient spinal anesthesia.

A comparison of ropivacaine with fentanyl to bupivacaine with fentanyl for postoperative patient-controlled epidural analgesia

Ropivacaine for patient-controlled epidural analgesia (PCEA) may facilitate postoperative patient mobilization because it causes less motor block than bupivacaine. Forty patients undergoing abdominal surgery were randomized in a double-blinded manner to the following: 0.05% bupivacaine/4 &mgr;g fentanyl, 0.1% bupivacaine/fentanyl, 0.05% ropivacaine/fentanyl, or 0.1% ropivacaine/fentanyl for standardized PCEA. We measured pain scores, side effects, and PCEA consumption for 42 h. Lower-extremity motor function was assessed with electromyography and isometric force dynamometry. Analgesia was equivalent among groups. Local anesthetic use was more in the 0.1% Ropivacaine and 0.1% Bupivacaine groups (77% increase, P = 0.001). Motor function decreased during PCEA (10%–35% decrease from preoperative, P < 0.001) and was equivalent among groups. Eight patients were transiently unable to ambulate. These patients used more local anesthetic (45 vs 33 mg mean, P < 0.05) with additional decrease in motor function (32%, P < 0.004) compared with ambulating patients. Other side effects were mild and equivalent among solutions. PCEA with bupivacaine/fentanyl and ropivacaine/fentanyl as 0.05% or 0.1% solutions appears clinically equipotent. Lower-extremity motor function decreases, but is unlikely to result in prolonged inability to ambulate. Use of a 0.05% solution may be advantageous to decrease local anesthetic use and prevent transient motor block.

NEW DEVELOPMENTS IN SPINAL ANESTHESIA

Spinal anesthesia can be used effectively and efficiently for a variety of cases in both the inpatient and the ambulatory surgery setting. Choice of agent, dose, distribution, use of adjuncts, and occasionally the use of continuous spinal anesthesia can tailor the spinal anesthetic to a specific type and duration of surgery. Although spinal anesthesia is extremely safe, adherence of new guidelines for patients receiving anticoagulant drugs, LMWH in particular, may minimize the risk of neurologic injury from spinal bleeding. At present, intrathecal adjuncts, such as neostigmine and clonidine used with local anesthetics, have shown limited usefulness, whereas lipophilic opioids, such as fentanyl, appear to increase duration and quality of spinal block without increasing the time to recovery. In the future, shorter-acting local anesthetics, possibly in conjunction with continuous catheter technologies, may reduce recovery times after spinal anesthesia without increasing risk. Spinal agents with long-acting analgesic properties that do not produce sensorimotor deficits may go beyond the immediate perioperative period and relieve postoperative pain. Currently there is controversy surrounding the use of spinal lidocaine and the occurrence of TNS, especially in the outpatient setting. The prudent use of small-dose bupivacaine and possibly procaine may reduce this risk, further supporting the use of spinal anesthesia for ambulatory as well as inpatient surgical procedures.