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Background General anesthetics-induced changes of electrical oscillations in the basal ganglia may render the identification of the stimulation targets difficult. The authors hypothesized that while sevoflurane anesthesia entrains coherent lower frequency oscillations, it does not affect the identification of the subthalamic nucleus and clinical outcome. Methods A cohort of 19 patients with Parkinson’s disease with comparable disability underwent placement of electrodes under either sevoflurane general anesthesia (n = 10) or local anesthesia (n = 9). Microelectrode recordings during targeting were compared for neuronal spiking characteristics and oscillatory dynamics. Clinical outcomes were compared at 5-yr follow-up. Results Under sevoflurane anesthesia, subbeta frequency oscillations predominated (general vs. local anesthesia, mean ± SD; delta: 13 ± 7.3% vs. 7.8 ± 4.8%; theta: 8.4 ± 4.1% vs. 3.9 ± 1.6%; alpha: 8.1 ± 4.1% vs. 4.8 ± 1.5%; all P < 0.001). In addition, distinct dorsolateral beta and ventromedial gamma oscillations were detected in the subthalamic nucleus solely in awake surgery (mean ± SD; dorsal vs. ventral beta band power: 20.5 ± 6.6% vs. 15.4 ± 4.3%; P < 0.001). Firing properties of subthalamic neurons did not show significant difference between groups. Clinical outcomes with regard to improvement in motor and psychiatric symptoms and adverse effects were comparable for both groups. Tract numbers of microelectrode recording, active contact coordinates, and stimulation parameters were also equivalent. Conclusions Sevoflurane general anesthesia decreased beta-frequency oscillations by inducing coherent lower frequency oscillations, comparable to the pattern seen in the scalp electroencephalogram. Nevertheless, sevoflurane-induced changes in electrical activity patterns did not reduce electrode placement accuracy and clinical effect. These observations suggest that microelectrode-guided deep brain stimulation under sevoflurane anesthesia is a feasible clinical option. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background:Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker that produces prolonged local anesthesia in animals and humans. Under a Food and Drug Administration–approved phase 1 Investigational New Drug trial, the authors evaluated safety and efficacy of NeoSTX alone and combined with 0.2% bupivacaine (Bup) with and without epinephrine.Methods:The authors conducted a double-blind, randomized, controlled trial involving healthy male volunteers aged 18 to 35 yr receiving two 10-ml subcutaneous injections. Control sites received Bup. In part 1, active sites received (1) 5 to 40 μg NeoSTX+Saline (NeoSTX-Saline), (2) 5 to 40 μg NeoSTX+Bup (NeoSTX-Bup), or (3) placebo (Saline). In part 2, active sites received 10 or 30 μg NeoSTX+Bup+Epinephrine (NeoSTX-Bup-Epi) or placebo. Primary outcome measures were safety and adverse events associated with NeoSTX. Secondary outcomes included clinical biochemistry, NeoSTX pharmacokinetics, and cutaneous hypoesthesia.Results:A total of 84 subjects were randomized and completed the two-part trial with no serious adverse events or clinically significant physiologic impairments. Perioral numbness and tingling increased with NeoSTX dose for NeoSTX-Saline and NeoSTX-Bup. All symptoms resolved without intervention. NeoSTX-Bup-Epi dramatically reduced symptoms compared with other NeoSTX combinations (tingling: 0 vs. 70%, P = 0.004; numbness: 0 vs. 60%, P = 0.013) at the same dose. Mean peak plasma NeoSTX concentration for NeoSTX-Bup-Epi was reduced at least two-fold compared with NeoSTX-Saline and NeoSTX-Bup (67 ± 14, 134 ± 63, and 164 ± 81 pg/ml, respectively; P = 0.016). NeoSTX-Bup showed prolonged cutaneous block duration compared with Bup, NeoSTX-Saline, or placebo, at all doses. Median time to near-complete recovery for 10 μg NeoSTX-Bup-Epi was almost five-fold longer compared with Bup (50 vs. 10 h, P = 0.007).Conclusion:NeoSTX combinations have a tolerable side effect profile and appear promising for prolonged local anesthesia.

Anesthesia care for the patients undergoing ophthalmologic surgical procedures during local/regional anesthesia balances goals of patient comfort with safety and an optimal outcome in a highly cost-conscious environment. This article discusses current practices and trends in anesthesia care with respect to sedation for eye surgery during local/regional anesthesia. Although there is no evidence that one local/regional anesthesia technique or sedation analgesia regimen is superior to the others, this review highlights important differences between these varied approaches. The type of block used for the ophthalmologic surgery alters the sedation requirements. Changes in surgical techniques have increased the popularity of topical anesthesia, which reduces the need for sedation analgesia and may lessen the need for an anesthesia practitioner. The involvement of an anesthesia practitioner in eye surgery varies from facility to facility based on costs, anesthesiologist availability, and local standards. Anesthesia care choices are often made based on surgeon skill and anesthesiologist comfort, as well as the expectations and needs of the patient.

Background: QX-314 is a quaternary lidocaine derivative considered to be devoid of clinically useful local anesthetic activity. However, several reports document that extracellular QX-314 application affects action potentials. Hence, the authors tested the hypothesis that QX-314 could produce local anesthesia in animal models in vivo. Methods: The authors tested QX-314 (10, 30, and 70 mM )i n three standard in vivo local anesthetic animal models, using a randomized, blinded experimental design with negative (placebo) and positive (70 mM lidocaine) controls. The guinea pig intradermal wheal assay (n 29) was used to test for peripheral inhibition of the cutaneous trunci muscle reflex, the mouse tail-flick test (n 30) was used to test for sensory blockade, and the mouse sciatic nerve blockade model (n 45) was used to test for motor blockade. Results: In all three animal models, QX-314 concentrationdependently and reversibly produced local anesthesia of long duration, at concentrations equivalent to those clinically relevant for lidocaine. In the guinea pig intradermal wheal assay, QX-314 produced peripheral nociceptive blockade up to 6 times longer than lidocaine (650 171 vs. 100 24 min [mean SD]; n 6 per group; P < 0.0001). In the mouse tail-flick test, QX-314 produced sensory blockade up to 10 times longer than lidocaine (540 134 vs. 50 11 min; n 6 per group; P < 0.0001). Finally, in the mouse sciatic nerve model, QX-314 produced motor blockade up to 12 times longer compared with lidocaine (282 113 vs. 23 10 min; n 9 or 10 per group; P < 0.0001). The onset of QX-314‐mediated blockade was consistently slower compared with lidocaine. Animals injected with saline exhibited no local anesthetic effects in any of the three models. Conclusion: In a randomized, controlled laboratory study, the quaternary lidocaine derivative, QX-314, concentration-dependently and reversibly produced long-lasting local anesthesia with a slow onset in animal models in vivo. The authors’ results raise the possibility that quaternary ammonium compounds may produce clinically useful local anesthesia of long duration in humans and challenge the conventional notion that these agents are ineffective when applied extracellularly. LOCAL anesthetic research during the past four decades has demonstrated that amino-ester and amino-amide local anesthetics block the generation and propagation of action potentials via an intracellular site of action at the voltage-gated Na channel. 1– 4 Many of the underlying experiments were performed using QX-314 (lidocaine N-ethyl chloride; N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium chloride; molecular weight, 298.9), a lidocaine derivative whose sole structural difference to the mother compound is in the presence of an additional N-ethyl group. This permanently renders the amino group quaternary, i.e., positively charged. As a result, the agent cannot readily pass biologic membranes. Indeed, a series of in vitro experiments where QX-314 was applied extracellularly found this agent to be ineffective in blocking action potentials. 5– 8 In contrast, intracellular application of QX-314 to peripheral and central neurons produces marked local anesthetic actions, blocking both fast, Na-dependent action potentials and voltage-dependent, noninactivating Na conductances. 5–10 However, various studies on a range of other quaternary cationic compounds have shown that these can block electrical conductances in axons when applied outside of the cell. Such studies involved QX572, 11,12 quaternary tropine esters, 7,13 tonicaine, 14 –16

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.

Background An initial pilot study of 300 sub-Tenon local anesthetic blocks (STBs) for intraocular surgery established the effectiveness and patient acceptability of the technique. Following this, a decision was made in 1995 to change from sharp needle techniques to STB for all eye surgeries performed during local anesthesia at Auckland Hospital (Auckland, New Zealand) by reeducation of anesthetists and surgeons. At this point, sufficient data were not available to confirm that STB would avoid the complications associated with the passage of sharp needles into the orbit or would cause a different set of serious complications. Methods A prospective study of the next 6,000 consecutive STBs performed at Auckland Hospital was carried out over a period of 6 yr (from 1995 to 2000). Results Sub-Tenon block is very effective, with a surgeon and patient acceptability rate of 98.8%. Insertion of the sub-Tenon cannula and administration of the anesthetic produces minimal discomfort, being completely painless in 68.8% of cases. There were no serious block-related complications in this series, supporting the safety of the sub-Tenon technique. Conclusion The experience at Auckland Hospital provides further support for the avoidance of passing sharp needles into the orbit.

Intravenous administration of halogenated and nonhalogenated ether and nonether alkane (“volatile”) anesthetics has been explored for more than a century.1 Of note, the earliest evaluations were in humans.2–6 One immediate and significant challenge was formulation. Early endeavors simply dissolved the anesthetics in aqueous solutions, but low solubility and side effects were problematic. A variety of oil-in-water emulsions were tried, with the first successes described 50 yr ago.2 In the present issue of Anesthesiology, Jee et al describe a novel “fat free” approach to formulating a volatile anesthetic (sevoflurane) emulsion, and the intravenous anesthetic delivery which it enabled.7 Volatile anesthetics formulated as emulsions in Intralipid or other fats have been shown to produce general anesthesia. Anesthesia could be induced with an emulsion, and once achieved, maintained by continuous infusion or by rebreathing.2–6,8,9 Not surprisingly, induction time was shorter with intravenous compared with inhaled volatile anesthetics.9,10 The minimum alveolar concentration of emulsified volatile anesthetics was significantly lower than that of inhaled anesthetics, attributed in part to effects of the intravenous lipid load on the blood:gas partition coefficient, but measured but blood concentrations were equivalent.9,10 Recovery time after emulsified volatile anesthetics was also rapid,10,11 and emulsion formulation was reported to not affect the time course of isoflurane washout.10 Volatile anesthetic emulsions have also been shown to elicit other, more “nontraditional” effects caused by inhaled volatile anesthetics. Emulsified isoflurane and sevoflurane in anesthetic and subanesthetic concentrations were cardioprotective against reperfusuion injury when administered intravenously,12–15 or in cardioplegia solution.16 Volatile anesthetics, encapsulated in lecithin microdroplets and injected intradermally, produced long-duration local anesthesia lasting several days in humans.17,18 Volatile anesthetic emulsions have also been reported to produce epidural anesthesia in rabbits,19 reversible conduction block in toad sciatic nerve,20 and intravenous regional anesthesia in rats.21 Nevertheless, as summarized in this issue’s Anesthesiology article by the research team from the Departments of Anesthesiology and Chemistry and the Division of Pharmaceutical Sciences at the University of Wisconsin, volatile anesthetic emulsions formulated in Intralipid or other fats have been limited by solubility, carrying capacity, and stability. In a previously reported effort to improve the amount of sevoflurane stably emulsified, the Wisconsin team created a copolymer (designated F13M5)-based surfactant nanoemulsion which could dissolve up to 20% sevoflurane by volume.22 The sevoflurane emulsion, when injected intavenously, induced general anesthesia in rats and dogs with rapid onset and recovery.22,23 However, the F13M5-based sevoflurane emulsion was accompanied by significant hypotension in the dogs, due to histamine release.23 Moreover, in additional studies reported in this issue of Anesthesiology, long-term stability testing of the original F13M5-based emulsion showed it to be unstable, leading to nanoparticle aggregation and formation of unacceptably large particles. The histamine release and formulation stability were significant safety issues necessitating a new formulation approach. The investigators now report the successful formulation of sevoflurane with a newly developed polymer, forming a nanoemulsion containing 20% sevoflurane by volume.7 The new emulsion was stable for over 1 yr when stored at 4°C, and, when injected intravenously, produced general anesthesia in rats with rapid onset and recovery. This new emulsion formulation of sevoflurane should facilitate additional investigations evaluating intravenous volatile anesthetic pharmacology, and the potential clinical application and utility of such a formulation. Existence of a stable formulation may obviate the need for preparing emulsions on a daily or frequent basis. Additional mechanistic investigations, such as those evaluating sites (brain vs. spinal cord) of anesthetic action,24,25 organ protection and modulation of ischemia-reperfusion injury, and neuraxial or regional anesthesia, may be facilitated. Like many articles, the one by Jee, et al prompts several obvious and non-obvious questions, and points the way to future investigations by which to seek the answers. For example, what are the fate, effect, and safety of the excipients and co-formulation agents in the sevoflurane emulsion? How will the pharmacokinetics and pharmacodynamics of the new intravenous sevoflurane compare with that of inhaled sevoflurane or other volatile anesthetics? While emulsions can obviously change the route of volatile anesthetic administration, will they influence the route and kinetics of elimination - pulmonary clearance and exhalation? Can the new sevoflurane emulsion be used for maintenance of anesthesia? How will exhaled intravenous volatile anesthetics be scavenged? If an anesthetic circuit is needed for scavenging, does this obviate one potential advantage of emulsions of not needing an anesthesia machine? Or can available nonanesthesia machine-based scavenging masks, which can also provide oxygen, be used? What are the relative advantages and disadvantages of intravenous emulsion versus inhalation-based administration of volatile anesthetics? Might intravenous anesthetic emulsions lead to new clinical indications in addition to that for which volatile anesthetics were originally approved? We can hopefully look forward to future investigations addressing these, and other questions. In addition to the specific implications for anesthesiology research and possibly practice, the manuscript by Jee et al also serves to remind us of issues relevant to innovation. Thus this editorial could have easily been titled “Sevoflurane emulsions: Informing nano-scale science and macro-scale science policy.” Innovation in pharmaceutical development can be considered radical or incremental, where the former involves development of new molecular entities while the latter includes supplemental indications and new formulations.26 Another interesting aspect of the pharmaceutical innovation published by Jee et al is that it comes from an academic laboratory. Should academic anesthesia be engaged in pharmaceutical development? Should academia in general? Indeed, the role of academia in innovation, entrepreneurship, and commercialization is currently controversial. Is this like getting oil and water to mix? “Purists” may argue that academia is the domain of basic, rather than applied research. Nevertheless, logic and evidence contravene such contentions. Whereas early constructs considered basic and applied research either exclusive and in conflict, or arrayed on either ends of a linear one-dimensional continuum, more informed paradigms consider them dynamic and intertwined.27 University innovation and technologies result in the introduction of hundreds of new products to the marketplace and billions of dollars of benefit to the US economy annually, and the creation of more than one new startup company per day.28 Indeed, approximately one-third of the scientifically innovative drugs approved by the US Food and Drug Administration from 1998 to 2007 were initially discovered in universities.29 Moreover, applied and commercialization research does not detract from traditional academic missions. Research shows that intellectual property creation and commercialization does not make faculty less likely to publish (on the contrary, they are more prolific), shift effort away from fundamental research toward more applied research, significantly delay publication, or replace scholarly output and quality as principal criteria for academic employment and advancement.28 The research and the report by Jee et al, together with the publication record of these investigators, confirm these contentions. Other academic anesthesia laboratories have likewise contributed to radical or incremental pharmaceutical innovation with commercialization potential,30–32 and such endeavors are to be encouraged. In summary, the report by Jee et al describes a new, enabling technology for the formulation of sevoflurane, and perhaps other, volatile anesthetic emulsions, which are stable when stored for up to a year. Such emulsions can be administered intravenously to rapidly achieve general anesthesia. Other potential applications may also be discovered. We look forward to additional investigations of volatile anesthetic emulsions.

Background The trend toward day-case surgery, with discharge on oral medication, has highlighted the need for effective and safe analgesics that facilitate a rapid recovery and discharge time. This study evaluated the analgesic efficacy, dose dependency, duration of action, and safety of the cyclooxygenase-2 specific inhibitor, valdecoxib, administered before oral or orthopedic surgery. Methods Eligible healthy adult patients were scheduled to undergo either extraction of two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with local anesthesia in two randomized, double-blind, placebo-controlled studies conducted at three centers in the United States. Patients received a single, preoperatively administered oral dose of placebo or 10 (oral surgery only), 20, 40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a 24-h treatment period, or until the patient required rescue medication. Efficacy measures included time to rescue medication, proportion of patients requiring such rescue, pain intensity, and the Patient's Global Evaluation of Study Medication. Results In both studies, all doses of valdecoxib produced analgesia with a duration (time to rescue analgesia) and magnitude (Pain Intensity, Patient's Global Evaluation) significantly greater than placebo. A dose-dependent effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no additional analgesic benefit. In both models, all doses of valdecoxib were well tolerated, with no clinically significant treatment-related gastrointestinal, renal, or platelet-derived adverse events, and no evidence of a dose-related increase in adverse events. Conclusions Preoperative orally administered valdecoxib provides well-tolerated and effective analgesia for mild to moderate postoperative pain.

Background Local anesthesia has been traditionally associated with blockade of voltage-sensitive sodium (Na(+)) channels. Yet in vitro evidence indicates that local anesthetic mechanisms are more complex than previously understood. For example, local anesthetics bind and allosterically modify 1,4-dihydropyridine-sensitive Ca(++) channels and can reduce Ca(++) influx in tissues. The current study examines the influence of voltage-sensitive Ca(++) channels in bupivacaine infiltration anesthesia. Methods Baseline tail-flick latencies to radiant heat nociception were obtained before subcutaneous infiltration of bupivacaine and Ca(++)-modulating drugs in the tails of mice. No musculature is contained in the tail that could result in motor block. The magnitude of infiltration anesthesia over time, as well as the potency of bupivacaine alone or in the presence of Ca(++)-modulating drug, was assessed by obtaining test latencies. Results The 1,4-dihydropyridine L-type Ca(++) channel agonist S(-)-BayK-8644 reduced the duration of action and potency of bupivacaine anesthesia. In opposite fashion, nifedipine and nicardipine increased the effects of bupivacaine. Neither nifedipine nor nicardipine alone elicited anesthesia. Alternatively, the phenylalkylamine L-type blocker verapamil elicited concentration-dependent anesthesia. Other Ca(++) channel subtype blockers were investigated as well. The N-, T-, P-, and Q-type channel blockers, omega-conotoxin GVIA, flunarizine, omega-agatoxin IVA, and omega-conotoxin MVIIC, respectively, were unable to modify bupivacaine anesthesia. Conclusions These results indicate that heat nociception stimulates Ca(++) influx through L-type channels on nociceptors in skin. Although other voltage-sensitive Ca(++) channels may be located on skin nociceptors, only the L-type channel drugs affected bupivacaine in the radiant heat test.

Background Lidocaine inhalation attenuates histamine-induced bronchospasm while evoking airway anesthesia. Because this occurs at plasma concentrations much lower than those required for intravenous lidocaine to attenuate bronchial reactivity, this effect is likely related to topical airway anesthesia and presumably independent of the specific local anesthetic used. Therefore, the authors tested the effect of dyclonine, lidocaine, and ropivacaine inhalation on histamine-induced bronchospasm in 15 volunteers with bronchial hyperreactivity. Methods Bronchial hyperreactivity was verified by an inhalational histamine challenge. Histamine challenge was repeated after inhalation of dyclonine, lidocaine, ropivacaine, or placebo on 4 different days in a randomized, double-blind fashion. Lung function, bronchial hyperreactivity to histamine, duration of local anesthesia, and lidocaine and ropivacaine plasma concentrations were measured. Statistical analyses were performed with the Friedman and Wilcoxon rank tests. Data are presented as mean +/- SD. Results The inhaled histamine concentration necessary for a 20% decrease of forced expiratory volume in 1 s (PC20) was 7.0 +/- 5.0 mg/ml at the screening evaluation. Lidocaine and ropivacaine inhalation increased PC20 significantly to 16.1 +/- 12.9 and 16.5 +/- 13.6 mg/ml (P = 0.007), whereas inhalation of dyclonine and saline did not (9.1 +/- 8.4 and 6.1 +/- 5.0 mg/ml, P = 0.7268). Furthermore, in contrast to saline and lidocaine, inhalation of both ropivacaine and dyclonine significantly decreased forced expiratory volume in 1 s from baseline (P = 0.0016 and 0.0018, respectively). The longest lasting and most intense anesthesia developed after dyclonine inhalation (48 +/- 13 vs. 28 +/- 8 [lidocaine] and 25 +/- 4 min [ropivacaine]). Conclusion Both lidocaine and the new amide local anesthetic ropivacaine significantly attenuate histamine-induced bronchospasm. In contrast, dyclonine, despite its longer lasting and more intense local anesthesia, does not alter histamine-evoked bronchoconstriction and irritates the airways. Thus, airway anesthesia alone does not necessarily attenuate bronchial hyperreactivity. Other properties of inhaled local anesthetics may be responsible for attenuation of bronchial hyperreactivity.

Background Peribulbar and retrobulbar anesthesia have long been opposed on the basis of the existence of an intermuscular membrane, which is supposed to separate the intraconal from the extraconal spaces in a water-tight fashion. A local anesthetic injected outside the cone should spread through this septum to reach the nerves to be blocked. The existence of this septum is questioned. The aim of this study was to compare the spread of a colored latex dye injected intraconally or extraconally to simulate both retrobulbar and peribulbar anesthesia. Methods The authors used 10 heads from human cadavers. For each head, one eye was injected intraconally, and the other eye was injected extraconally. The heads were then frozen and sectioned into thin slices following various planes. They were then photographed and observed. Results There was no evidence of the existence of an intermuscular septum separating the intraconal and extraconal spaces. Those two spaces appeared to be part of a common spreading space, the corpus adiposum of the orbit. Conclusions These results are in accord with the fact that clinical studies were not able to clearly demonstrate that retrobulbar anesthesia is more efficient than peribulbar anesthesia. On the basis of a similar clinical efficacy of the two techniques as a result of similar spreading of the local anesthetic injected, and a potentially higher risk of introducing the needle into the muscular cone, the authors recommend replacing retrobulbar anesthesia with peribulbar anesthesia.

Background Given the current practice environment, it is important to determine the anesthetic technique with the highest patient acceptance and lowest associated costs. The authors compared three commonly used anesthetic techniques for anorectal procedures in the ambulatory setting. Methods Ninety-three consenting adult outpatients undergoing anorectal surgery were randomly assigned to one of three anesthetic treatment groups: group 1 received local infiltration with a 30-ml mixture containing 15 ml lidocaine, 2%, and 15 ml bupivacaine, 0.5%, with epinephrine (1:200,000) in combination with intravenous sedation using a propofol infusion, 25-100 microg. kg-1. min-1; group 2 received a spinal subarachnoid block with a combination of 30 mg lidocaine and 20 microg fentanyl with midazolam, 1-2-mg intravenous bolus doses; and group 3 received general anesthesia with 2.5 mg/kg propofol administered intravenously and 0.5-2% sevoflurane in combination with 65% nitrous oxide. In groups 2 and 3, the surgeon also administered 10 ml of the previously described local anesthetic mixture at the surgical site before the skin incision. Results The mean costs were significantly decreased in group 1 ($69 +/- 20 compared with $104 +/- 18 and $145 +/- 25 in groups 2 and 3, respectively) because both intraoperative and recovery costs were lowest (P < 0.05). Although the surgical time did not differ among the three groups, the anesthesia time and times to oral intake and home-readiness were significantly shorter in group 1 (vs. groups 2 and 3). There was no significant difference among the three groups with respect to the postoperative side effects or unanticipated hospitalizations. However, the need for pain medication was less in groups 1 and 2 (19% and 19% vs. 45% for group 3; P < 0.05). Patients in group 1 had no complaints of nausea (vs. 3% and 26% in groups 2 and 3, respectively). More patients in group 1 (68%) were highly satisfied with the care they received than in groups 2 (58%) and 3 (39%). Conclusions The use of local anesthesia with sedation is the most cost-effective technique for anorectal surgery in the ambulatory setting.

Increased tolerance to cerebral ischemia produced by general anesthesia during temporary carotid occlusion. By B. A. Wells, A. S. Keats, and D. A. Cooley. Surgery 1963; 54:216-23. Local anesthesia with little or no preoperative sedation is currently recommended as the anesthetic of choice for temporary carotid occlusion during carotid endarterectomy. Purported advantages include minimal circulatory and respiratory changes from the local anesthetic, and constant verbal contact can be maintained with the patient so that neurologic changes are promptly recognized. However, local anesthesia may not be satisfactory in uncooperative or semiconscious patients. We therefore undertook a trial of general anesthesia in 56 consecutive patients undergoing carotid endarterectomy. Patients were induced in standardized fashion using intravenous thiopental (100-400 mg), atropine (0.2 mg), and succinylcholine (40-80 mg). Cyclopropane, along with deliberate hypercapnia and hypertension, was used for anesthesia maintenance. All patients tolerated carotid occlusion for periods of up to 30 min during general anesthesia without shunt, bypass, or hypothermia. Except for one patient, electroencephalogram evidence of cerebral ischemia was not apparent during occlusion, and no patient suffered postoperative neurologic sequela. Twenty percent of patients who had their carotid arteries occluded preoperatively for 30-60 s without general anesthesia suffered convulsions. These data suggest that general anesthesia increased the tolerance to cerebral ischemia. Potential mechanisms involved might include: 1) decreased cerebral metabolic rate for oxygen; 2) increased cerebral blood flow from hypercapnia; 3) increased arterial oxygen tension; and 4) recruitment of new routes of collateral circulation.

Background The optimal method to achieve analgesia after inguinal hernia repair in children is unknown. This study compared the analgesic efficacy, adverse events, and the costs associated with supplementation of local anesthesia (infiltration of the wound) with either intravenous ketorolac or caudal analgesia in children having inguinal hernia repair. Methods With parental consent and institutional review board approval, children aged 2-6 yr having elective, outpatient inguinal hernia repair were studied in this randomized, single-blinded investigation. Anesthesia was induced by inhalation with nitrous oxide and halothane or intravenously with propofol. Anesthesia was maintained with nitrous oxide and halothane. Patients were randomly assigned to receive caudal analgesia (1 ml/kg 0.20% bupivacaine with 1/200,000 epinephrine) or intravenous ketorolac (1 mg/kg) immediately after induction of anesthesia. Both groups received field blocks with 0.25% bupivacaine administered by the surgeon under direct vision during operation. Patients were assessed for 24 h. In-hospital pain was assessed using a behavior-based pain score. Parents assessed pain with a visual linear analog pain scale with anchors of 0 (no pain) and 100 (worst pain imaginable). Results The authors studied 164 children, with 84 patients in the ketorolac group. The groups had similar demographic data. In-hospital analgesic requirements and pain scores were almost identical in both groups. Pain at home was significantly less in the ketorolac group, with visual linear analog pain scale scores of 10 (0-80) compared with 20 (0-80) (median [range]) for ketorolac versus caudal (P = 0.002 by the Mann-Whitney U test). The ketorolac group also had a lower incidence of vomiting, ambulated more rapidly, and micturated earlier (P < 0.05). Conclusion The use of intravenous ketorolac to supplement local anesthesia infiltrated by the surgeon during pediatric inguinal hernia repair is superior to supplementation with caudal analgesia.

Background Recent evidence has suggested that the timing of administration of analgesic drugs could influence their efficacy by reducing the sensitization of the nervous system induced by the nociceptive inputs, but this concept of preemptive analgesia is still debated in both clinical and basic research. Methods The model of acute inflammatory pain induced by carrageenin was used to study the influence of timing of administration of bupivacaine (0.2 ml of a 0.5% solution with 0.005 mg/ml epinephrine) on the development of hyperalgesia, edema, and increase in temperature. The animals received bupivacaine 5 min before (BUPI PRE group, n = 20) or 60 min after (BUPI POST group, n = 20) carrageenin (1 ml/kg of 1% solution) was injected into the left hind paw. Two control groups (n = 15 in each) received saline 5 min before or 60 min after administration of carrageenin. Hyperalgesia of the injected paw was evaluated by the vocalization threshold to paw pressure, edema by measuring paw circumference with a thread, and plantar temperature with a thermocouple thermometer. All measurements were done before carrageenin injection then every 30 min thereafter for 240 min. Another series (n = 24), with the same four groups was also evaluated at 24 h. Results Local injection of bupivacaine 60 min after carrageenin partially reduced the edema and hyperalgesia. The injection of bupivacaine 5 min before carrageenin was more efficient than the delayed injection and reduced hyperalgesia, edema and the increase in temperature temporarily, but did not totally prevent their development. All groups were similar at 240 min and 24 h. Conclusions These results show that a slight advantage of infiltration with bupivacaine before injury exists in this carrageenin model of acute inflammatory pain. However, this benefit is limited in time and bupivacaine did not have any preemptive analgesic effect.

Background Studies of endovascular treatment for acute ischemic stroke have identified general anesthesia as a predictor for poor outcome in comparison with local anesthesia/sedation. This retrospective study attempts to identify modifiable factors associated with poor outcome, while adjusting for baseline stroke severity, in patients receiving general anesthesia. Methods We reviewed charts of 129 patients treated between January 2003 and September 2009. The primary outcome was the modified Rankin Score of 0-2 for 3 months poststroke. Predictors of neurologic outcome included baseline National Institutes of Health Stroke Scale score, blood glucose concentration, and age. Additional risk factors evaluated were prolonged stroke onset-treatment interval and systolic blood pressure less than 140 mmHg. Choice of local anesthesia or general anesthesia was recorded. Results The study group was 96 out of 129 patients for whom modified Rankin Scale scores were available; 48 patients received general anesthesia and 48 local anesthesia. The proportion of patients with "good" outcomes were 15% and 60% in the general anesthesia group and local anesthesia group, respectively (P < 0.001). Lowest systolic blood pressure and general anesthesia were correlated (r = -0.7, P < 0.001). Independent predictors for good neurologic outcome were local anesthesia, systolic blood pressure greater than 140 mmHg, and low baseline stroke scores. Conclusions Adjusted for stroke severity, patients who received general anesthesia for treatment are less likely to have a good outcome than those managed with local anesthesia. This may be due to preintervention risk not included in the stroke severity measures. Hypotension, more frequent in the general anesthesia patients, may also contribute.

In a double-blinded, randomized, prospective multi-center study of 695 women, we investigated whether epidural injection of sufentanil added to 0.125% bupivacaine with epinephrine (1:800,000) reduces the total amount of local anesthetic required, resulting in less motor blockade and reduced incidence of instrumental deliveries, and improves the quality of analgesia provided by this low concentration of local anesthetic without jeopardizing the safety of the baby. In addition, other potential benefits of sufentanil (such as decrease in the incidence of shivering) and side effects were examined. It was found that adding incremental doses of 10 micrograms sufentanil up to a maximum of 30 micrograms reduced the incidence of instrumental deliveries from 36 to 24% (P less than 0.01) and significantly improved quality and duration of analgesia without depressing the neurobehavioral status of the baby. No other benefits from adding sufentanil were found. The only side effect that occurred more frequently after sufentanil was pruritus. We conclude that epidural injection of 10-30 micrograms sufentanil added to 0.125% bupivacaine with epinephrine (1:800,000) improved the quality of analgesia during labor and reduced the incidence of instrumental deliveries without jeopardizing the safety of the baby.

This study compared the effectiveness of 0.5% ropivacaine and 0.5% bupivacaine for brachial plexus block. Forty-eight patients received a subclavian perivascular brachial plexus block for upper-extremity surgery. One group (n = 24) received ropivacaine 0.5% (175 mg) and a second group (n = 24) received bupivacaine 0.5% (175 mg), both without epinephrine. Onset times for analgesia and anesthesia in each of the C5 through T1 brachial plexus dermatomes did not differ significantly between groups. Duration of analgesia and anesthesia was long (mean duration of analgesia, 13-14 h; mean duration of anesthesia, 9-11 h) and also did not differ significantly between groups. Motor block was profound, with shoulder paralysis as well as hand paresis developing in all of the patients in both groups. Two patients in each group required supplemental blocks before surgery. Ropivacaine 0.5% and bupivacaine 0.5% appeared equally effective in providing brachial plexus anesthesia.

To compare the efficacy and side effects of 0.2 mg intrathecal (IT) morphine with 0.125% epidural bupivacaine, 62 women in labor were studied. They were randomly divided into three groups: group 1 (n = 20) received IT morphine; group 2 (n = 22) received epidural bupivacaine; and group 3 (n = 20) received a combination of both using a combined spinal-epidural (CSE) technique. According to a visual analogue scale for assessing analgesia, neither IT 0.2 mg morphine nor 10 ml 0.125% epidural bupivacaine was effective in producing adequate pain relief in labor, whereas the combination produced excellent analgesia. The use of IT morphine significantly reduced the dosage requirement of epidural bupivacaine. The incidence of nausea, vomiting, and pruritus was significantly higher when IT morphine had been administered, whereas that of urinary retention did not differ. No serious respiratory depression occurred in any of the patients. When the course of labor was studied, the prior use of IT morphine significantly prolonged the duration of the first stage of labor and the total duration of labor. We conclude that the administration of 0.2 mg IT morphine in combination with epidural administration of 0.125% bupivacaine provides better analgesia than the administration of either drug alone.

In order to evaluate the role of the pharmacokinetics of the age-related changes in the clinical profile of spinal anesthesia with bupivacaine, we studied the influence of age on the systemic absorption and systemic disposition of bupivacaine after subarachnoid administration in 20 male patients (22-81 yr), ASA Physical Status 1 or 2, by a stable isotope method. After subarachnoid administration of 3 ml 0.5% bupivacaine in 8% glucose, a deuterium-labeled analog (13.4 mg) was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of unlabeled and deuterium-labeled bupivacaine were determined with a combination of gas chromatography and mass fragmentography. Biexponential functions were fitted to the plasma concentration-time data of the deuterium-labeled bupivacaine. The systemic absorption was evaluated by means of deconvolution. Mono- and biexponential functions were fitted to the data of fraction absorbed versus time. The maximal height of analgesia and the duration of analgesia at T12 increased with age (r = 0.715, P less than 0.001; r = 0.640, P less than 0.01, respectively). In 18 patients the systemic absorption of bupivacaine was best described by a biexponential equation. The half-life of the slow systemic absorption process (r = -0.478; P less than 0.05) and the mean absorption time (r = -0.551; P less than 0.02) decreased with age. The total plasma clearance decreased with age (r = -0.650, P less than 0.002), whereas the mean residence time and terminal half-life increased with age (r = 0.597, P less than 0.01; r = 0.503, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

THE rare but devastating complication of cauda equina syndrome (CES) after spinal anesthesia has been reported with several local anesthetics, most frequently lidocaine. 1 A separate complication of spinal anesthesia, transient neurologic syndrome (TNS), consisting of potentially severe but transient lumbosacral pain, has also been reported and is also most frequent with lidocaine. 2 The mechanism of CES from local anesthesia is most likely necrotic or apoptotic neuronal death, depending on the intensity of the local anesthetic exposure. 3 The mechanism of TNS is unknown but seems to be distinct from that of CES. 4,5 Lidocaine's pharmacokinetics are ideal for spinal anesthesia for short-duration, ambulatory surgery. The increased frequency of CES and TNS with lidocaine has encouraged the study of other local anesthetics to substitute for lidocaine, without complete success. 6-8 Procaine has been reported to be less likely to produce TNS than lidocaine, with a kinetic profile also suitable for short-duration surgery. 9,10 However, there has been no modem study of procaine and CES. We now report a case of permanent CES after procaine spinal anesthesia.

This study compared the effects of general and regional anesthesia on cognitive and psychosocial functioning in elderly persons. Sixty-four patients between 60 and 86 yr of age undergoing knee arthroplasty were randomly assigned to receive either general or regional anesthesia. A battery of psychometric tests, including the Satz-Mogel form of the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised and the Sickness Impact Profile, and various neuropsychological measures were administered by a blinded observer just before surgery and again 3 months later. Analyses of covariance revealed improvements in most measures that were equivalent between groups. The results indicated that there were no cognitive or psychosocial effects of general or regional anesthesia after 3 months in elderly persons undergoing knee arthroplasty. In this patient population, general anesthesia poses no more risk to long-term mental function than regional anesthesia.

A potentially serious complication of long-term epidural catheterization in cancer patients is infection. The early signs of infection were studied in 350 patients in whom long-term epidural catheters were inserted. Three areas of the catheter track were found to be involved; exit site and superficial catheter track infection, and epidural space infection. The authors identified the early signs of infection in each area and the progress of the infection from the deep track to include the epidural space in four of these patients. All 19 patients who developed deep track or epidural infections were successfully treated with antibiotics and catheter removal. None of the patients required surgery for spinal cord decompression. Catheters were replaced in 15 of the 19 treated patients who requested them after treatment with no recurrent infections. It was concluded that use of long-term epidural catheterization is associated with a definable epidural infection rate. The use of epidural opioid analgesia is an effective and safe means of obtaining pain relief for terminally ill patients when patients are monitored for possible infection and receive prompt treatment when the diagnosis is established.

To determine the incidence and duration of hypoxemia in the postanesthesia care unit (PACU), 200 patients were investigated in a single-blind observer study. The number of unrecognized hypoxemic episodes, as well as risk factors and possible association between hypoxemia and postoperative morbidity, were studied. Oxygenation was monitored continuously with a pulse oximeter. One or more hypoxemic episodes (SpO2 less than or equal to 90%) were noted in 55% of the patients. SpO2 values less than or equal to 80% were noted in 13% of the patients. Supplementary oxygen was given during 55% of the 447 hypoxemic episodes registered. The hypoxemic episodes were unrecognized by the staff in 95% of the cases. With stepwise multiple logistic regression analyses, risk factors associated with a higher incidence of hypoxemia were: duration of anesthesia (P less than 0.0001), age (P less than 0.002) and a history of smoking (P less than 0.01). Patients who had undergone regional anesthesia had a lower risk of hypoxemia (P less than 0.0002). The occurrence of hypoxemia in the PACU could not be correlated to postoperative morbidity. We conclude that hypoxemic episodes in our PACU are common and that the routine use of supplemental oxygen combined with normal clinical surveillance did not prevent hypoxemic episodes.

To evaluate whether, and to what extent, release of endogenous vasopressin supports blood pressure when efferent sympathetic drive is blocked by epidural anesthesia, the authors studied the effects of high epidural anesthesia alone and when vasopressin was prevented from acting at its vascular (V1)-receptor in six awake, trained, unsedated dogs. On different days, the same dose of 0.5% bupivacaine (8–13 ml) was injected epidurally in a randomized fashion either in the presence or absence of (V1)-vasopressin receptor blockade, and the effects were evaluated on cardiovascular (arterial blood pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, and on plasma concentrations of vasopressin and renin. Results were also contrasted to those obtained after epidural injection of saline alone (placebo) in the same dogs. When endogenous vasopressin was prevented from acting by intravenous pretreatment with a specific V1-receptor antagonist (β-mercapto-β, β-cyclopenta-methylene-propionyl-O-Me-Tyr-Arg-Vasopressin), epidural anesthesia resulted in a rapid and sustained 35% decrease in mean arterial blood pressure from 92 mmHg ± 5 SE to 60 mmHg ± 4. In contrast, only a 14% decrease in mean blood pressure from 92 mmHg ± 5 to 79 mm Hg ± 6 was noted after epidural anesthesia alone. This difference between groups was statistically significant (P = 0.0001). The V1-receptor blockade alone had no detectable effect. Vasopressin plasma concentrations significantly increased from 3.4 ± 0.3 pg ± ml-1 to 16.2 ± 3.2 pg ± ml-1 after epidural anesthesia but did not change after epidural saline. Renin activity did not change significantly in any group despite the marked hypotension observed after combined sympathetic and vasopressin blockade. Thus, in awake, unsedated dogs, blockade of most, if not all, efferent sympathetic drive by epidural anesthesia 1) is associated with hemodynamically effective increases in vasopressin concentrations, most likely to compensate for decreased cardiac filling or arterial pressure, and induces severe hypotension when endogenous vasopressin is prevented from acting at its V1-receptor; and 2) suppresses the neurally mediated renin release known to occur in response to hypotension. The authors conclude that among the hormonal systems that can support arterial pressure, an intact vasopressin system plays an important role when spinal sympathetic outflow is selectively and markedly attenuated by high epidural anesthesia.

The authors performed a clinical trial in 313 patients in labor to determine the safety and efficacy of an air test for unintentional intravenous placement of epidural catheters. Following routine aspiration for blood and cerebrospinal fluid, 1 ml of air was injected through each epidural catheter while heart tones were continually monitored with a Doppler ultrasound probe placed over the maternal precordium. In 281 patients, Doppler heart tones did not change following air injection (negative air test). All but eight of these patients developed an adequate level of analgesia following anesthetic administration, and no patients with negative air tests developed signs or symptoms of local anesthetic toxicity (false-negative rate, 0%; 95% confidence limits, 0.0-1.1%). Doppler heart tone changes followed air injection in 22 cases (positive air test). In 16 of these, intravenous catheter position was subsequently shown by aspiration of blood from the catheter or by the use of test doses consisting of local anesthetics with or without epinephrine. In six cases, adequate levels of analgesia developed despite a positive air test (false-positive rate, 2%; 95% confidence limit, 0.7-4.3%). None of the 303 patients receiving the air test developed any complications attributable to the injection of air (95% confidence limits, 0.0-1.0%). The authors conclude that air, with precordial Doppler detection, is a safe and effective test for identifying intravenously located epidural catheters.

80 women receiving spinal anesthesia for postpartum tubal ligation were entered into a double-blind randomized protocol which examined the effects of epinephrine on intrathecal fentanyl-induced postoperative analgesia. All patients received 70 mg hyperbaric lidocaine with either 0.2 mg epinephrine (LE) 10 mcg fentanyl (LF) epinephrine and fentanyl (LFE) or 0.4 ml saline (L). Onset and regression of anesthesia degree of intraoperative comfort incidence of pruritus and extent of postoperative analgesia were evaluated. The simultaneous administration of epinephrine and fentanyl prolonged the duration of complete analgesia (137 +or- 47 minutes [LFE]; 76 +or- 32 minutes [LE]; 85 +or-44 minutes [LF]; 65 +or-36 minutes [L]; and the duration of effective analgesia (562 +or-504 minutes [LFE]; 227 +or-201 minutes [LE]; 203 +or-178 minutes [LF]; 198 +or- 342 minutes [L]. Administration of epinephrine decreased the incidence of pruritus associated with intrathecal fentanyl (1/18 [LFE]; 1/21 [LE]; 8/19 [LF]; 2/19 [L]). (authors)

The authors tested the hypothesis that during epidural anesthesia: 1) shivering-like tremor is primarily normal thermoregulatory shivering; 2) hypothermia does not produce a subjective sensation of cold; and 3) injectate temperature does not influence tremor intensity. An epidural catheter was inserted into ten healthy, nonpregnant volunteers randomly assigned to skin-surface warming below the T10 dermatome (warmed group) or no extra warming (unwarmed group). Each volunteer was given two 30-ml epidural injections of 1% lidocaine (16.0 +/- 4.7 degrees C and 40.6 +/- 0.7 degrees C at the catheter tip), in random order separated by at least 3 h. Skin-temperature gradients (forearm-fingertip) and tympanic membrane and average skin temperatures were recorded; significant vasoconstriction was prospectively defined as a gradient greater than or equal to 4 degrees C. Integrated electromyographic (EMG) intensity was recorded from four upper-body muscles. Overall thermal comfort was evaluated using a visual analog scale. Tympanic membrane temperatures decreased significantly in the unwarmed group (n = 6). Tremor occurred following ten of 12 injections in unwarmed volunteers, but only following one of eight injections in the warmed group. Integrated EMG intensity did not differ significantly following epidural injection of warm and cold lidocaine: tremor started when tympanic membrane temperature decreased about 0.5 degrees C and continued until central temperature returned to within 0.5 degrees C of control. Tremor always was preceded by hypothermia and vasoconstriction in the arms. Thermal comfort increased in both groups after epidural injection, with maximal comfort occurring at the lowest tympanic temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-six former preterm infants undergoing inguinal hernia repair were studied. All were less than or equal to 51 weeks postconceptual age at the time of operation. Patients were randomly assigned to receive general or spinal anesthesia. Group 1 patients received general inhalational anesthesia with neuromuscular blockade. Group 2 patients received spinal anesthesia using 1% tetracaine 0.4-0.6 mg/kg in conjunction with an equal volume of 10% dextrose and 0.02 ml epinephrine 1:1000. In the first part of the study, infants randomized to receive spinal anesthesia also received sedation with im ketamine 1-2 mg/kg prior to placement of the spinal anesthetic (group 2 A). The remainder of group 2 patients did not receive sedation (group 2 B). Respiratory pattern and heart rate were monitored using an impedance pneumograph for at least 12 h postoperatively. Tracings were analyzed for evidence of apnea, periodic breathing and/or bradycardia by a pulmonologist unaware of the anesthetic technique utilized. None of the patients who received spinal anesthesia without ketamine sedation developed postoperative bradycardia, prolonged apnea, or periodic breathing. Eight of nine infants (89%) who received spinal anesthesia and adjunct intraoperative sedation with ketamine developed prolonged apnea with bradycardia. Two of the eight infants had no prior history of apnea. Five of the 16 patients (31%) who received general anesthesia developed prolonged apnea with bradycardia. Two of these five infants had no prior history of apnea. When infants with no prior history of apnea were analyzed separately, there was no statistically significant increased incidence of apnea in children receiving general versus spinal anesthesia with or without ketamine sedation. Because of the small numbers of patients studied, and the multiple factors that may influence the incidence of postoperative apnea (e.g., prior history of neonatal apnea), standard postoperative respiratory monitoring of these high-risk infants is still recommended following all anesthetic techniques.

A randomized, double-blind, placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor in nulliparous women. When the cervix was fully dilated, coded study solution was substituted for the known bupivacaine-fentanyl solution. The study solution for 29 patients was 0.0625% bupivacaine-0.0002% fentanyl; 34 patients received saline placebo. The two groups had similar pain scores during the first stage of labor. During the second stage, pain scores were significantly higher in the saline-placebo group at each 30-min interval between 60 and 150 min after the diagnosis of full cervical dilation. Similarly, there was a significant difference between the two groups in global assessment of analgesia quality during the second stage, but the difference occurred in those patients with a second-stage duration of greater than or equal to 60 min. Among the women who delivered vaginally, eleven of 28 (39%) women in the bupivacaine-fentanyl group, versus five of 34 (15%) in the saline-placebo group, had surgical perineal anesthesia for vaginal delivery (P less than .05). Six of 28 (21%) women in the bupivacaine-fentanyl group, and five of 34 (15%) in the saline-placebo group, underwent instrumental vaginal delivery (P = NS). The median duration of the second stage of labor was 53 min (range = 5-283) in the bupivacaine-fentanyl group, and 63 min (range = 16-181) in the saline-placebo group (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Clonidine may be administered intrathecally as an adjunct to local anesthetics or accidentally during attempted epidural analgesia. To examine clonidine's acute maternal and fetal effects, the authors injected clonidine (100, 300, 750, 1500 micrograms cumulative dose at 15-min intervals) intrathecally in nine chronically prepared near-term ewes. Unlike intrathecal saline injection, which did not alter any parameters, clonidine altered maternal blood pressure in a biphasic manner (depression at lower doses and return to baseline after the highest dose). Clonidine produced a dose-dependent decrease in maternal and fetal heart rate. After the highest dose, 1500 micrograms, PO2 decreased in both ewe and fetus, accompanied by fetal hypertension and bradycardia. Clonidine increased maternal and fetal serum glucose, but not cortisol. Although clonidine-induced hypoxemia and hyperglycemia occur only in sheep, fetal bradycardia may limit the usefulness of clonidine in large doses (greater than 10 micrograms/kg) in obstetrics. Lower doses, such as may be used to enhance spinal anesthesia, are well tolerated in sheep.

Epidural injection of drug combinations may decrease toxicity by decreasing the dose of each component, but may also result in detrimental drug interactions. In this study interactions among bupivaciane, fentanyl, epinephrine, 2-chloroprocaine, and lidocaine for epidural analgesia during labor were examined. In part 1 of the study, healthy parturients received in a random manner either 10 ml of 0.25% bupivacaine with 5 micrograms/ml fentanyl (n = 50), or 10 ml of this combination with 3.33 micrograms/ml freshly added epinephrine (n = 50). Epinephrine prolonged the median duration of pain relief (180 vs. 138 min, P less than 0.05) without affecting duration of first or second stages of labor, or neonatal Apgar scores. Blood pressure decreased slightly more in those receiving epinephrine, although the incidence of hypotension requiring treatment did not differ between groups. Part 2 of the study evaluated the possibility that local anesthetic used for confirming catheter tip location may interfere with the analgesic action of this bupivacaine-fentanyl-epinephrine (BFE) combination. In 50 additional parturients, a test dose of either 2-chloroprocaine (n = 25) or lidocaine (n = 25) was injected through the epidural catheter and was followed by injection of the BFE mixture. The lidocaine test dose group had a greater duration of analgesia than the 2-chloroprocaine test dose group (median duration of 164 vs. 91 min, P less than 0.05). The authors conclude that the addition of epinephrine 3.33 micrograms/ml significantly increases the duration of analgesia obtained from 0.25% bupivacaine with 5 micrograms/ml fentanyl. However, prior injection of 2-chloroprocaine, but not lidocaine, significantly decreases the duration of analgesia achieved with this BFE mixture.

To compare the analgesic efficacy and plasma concentration of intramuscular (IM) versus epidural (EP) clonidine, 20 patients recovering from orthopedic or perineal surgery were randomly divided into two groups of ten. Clonidine (2 micrograms/kg) was administered epidurally in group 1 and intramuscularly in group 2. Analgesia was assessed using a visual analog scale (VAS) over a period of 6 h following clonidine administration. Venous blood samples were obtained at specific intervals for radioimmunoassay determination of plasma clonidine concentrations. The maximum reduction in VAS pain score was 78.5 +/- 20.6% in the EP group and 68.1 +/- 31.5% in the IM group (NS). Onset of analgesia was similar (within 15 min of injection), but duration tended to be longer after epidural than intramuscular administration (208 +/- 87 min vs. 168 +/- 95 min, mean +/- SD, P greater than 0.05). The peak plasma clonidine concentration after EP injection was 0.82 +/- 0.22 ng/ml and 1.02 +/- 0.76 ng/ml after IM injection. Hypotension, bradycardia, and drowsiness occurred with both methods of administration. None of these effects required treatment. Thus, in postoperative patients clonidine produces similar analgesia and side effects after parenteral or EP administration.

To determine if age, height, weight, body mass index, or vertebral column length significantly influence the distribution of sensory analgesia or anesthesia after subarachnoid injection of hyperbaric bupivacaine, 52 women presenting for cesarean section were studied. All received 15 mg hyperbaric bupivacaine via subarachnoid injection at L-2 or L-3. Fifteen minutes after injection, while the women lay supine on a horizontal operating table, the maximum cephalad extent of sensory analgesia (loss of sensation of sharpness to pin prick) and anesthesia (loss of sensation of light touch) was determined. Age (20-42 yr), height (146.9-174.0 cm), weight (55.5-136.4 kg), body mass index (19.2-50.0 kg/m2), and vertebral column length (49.6-67.0 cm) did not correlate with the spread of sensory blockade. In conclusion, in parturients of age, height, weight, body mass index, and vertebral column length within the aforementioned ranges, it is not necessary to vary the dose of injected hyperbaric bupivacaine with changes in any of the patient variables studied.

A total of 2,511 patients who received spinal anesthesia for cesarean delivery were observed for the development of postdural puncture headache (PDPH); 804 patients received a mixture of tetracaine and procaine, 942 received bupivacaine-glucose, and 765 received lidocaine-glucose. They were observed for the development of PDPH for a minimum of 72 h. PDPH occurred in 9.54% of patients who received lidocaine-glucose during the first 36 h compared with 7.64% of patients who received bupivacaine-glucose and 5.85% of patients who received tetracaine-procaine. The differences between all groups was statistically significant. No differences were found in the percentage of patients who ultimately required epidural blood patch for relief of symptoms after 36 h.

This study examined the efficacy of patient-controlled epidural analgesia (PCEA) during labor and compared the suitability of three different PCEA solutions. After establishing effective epidural analgesia with 12 ml of 0.25% bupivacaine, 72 parturients in active labor were randomly assigned to one of four groups: physician-controlled continuous epidural infusion using 0.125% bupivacaine (CEI); PCEA using 0.125% bupivacaine (B); PCEA using 0.125% bupivacaine with fentanyl 1 micrograms/ml (BF); and PCEA using 0.125% bupivacaine with fentanyl 1 micrograms/ml and 1:400,000 epinephrine (BFE). The CEI infusion was begun at 12-16 ml/h and adjusted to maintain a T10 sensory level and adequate pain relief. PCEA pumps were programmed to deliver a 6 ml/h basal infusion, 4 ml on-demand boluses, 10-min lockout intervals between doses, and a 20 ml hourly limit. Hemodynamic parameters, sensory level, quality of analgesia, duration of labor, overall satisfaction, and Apgar scores did not differ among groups. Compared with CEI, PCEA with plain bupivacaine did not decrease total local anesthetic usage or average hourly infusion rates during labor. However, addition of fentanyl (groups BF and BFE) decreased hourly infusion requirements. Average hourly infusion rates were 13.0 +/- 1.1 ml/h (B), 10.6 +/- 0.6 ml/h (BF), and 9.6 +/- 0.5 ml/h (BFE); group B differs from others (P less than 0.05). No instance of respiratory depression or complication secondary to PCEA was observed. Mild pruritus occurred only with fentanyl-containing solutions, whereas dense motor block developed more frequently with the epinephrine-containing solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Background The currently used emulsion formulations of 1% propofol contain 10% soybean oil. However, a new emulsion of 1% propofol (Ampofol) containing 50% less lipid has recently become available for clinical investigation. This study was designed to compare the pharmacodynamic properties of Ampofol with those of a standard formulation (Diprivan) when administered for intraoperative sedation. Methods Sixty healthy outpatients undergoing minor operations with local anesthesia were randomly assigned to receive either Ampofol (n = 31) or Diprivan (n = 29) for intravenous sedation. The sedation was initiated with an intravenous loading dose of propofol, 0.75 mg/kg, followed by an initial infusion rate of 50 microg x kg(-1) x min(-1) to achieve an Observer's Assessment of Alertness/Sedation score of 3. The targeted level of sedation was maintained with a variable-rate propofol infusion during the operation. The onset times to achieving a sedation score of 3, the severity of pain on injection of the loading dose, intraoperative hemodynamic variables, and electroencephalographic Bispectral Index values were recorded. In addition, recovery times, postoperative pain and nausea, and patient satisfaction with the sedative medication were assessed. Results There were no significant differences between Ampofol and Diprivan with respect to onset times, dosage requirements, Bispectral Index values, hemodynamic variables, recovery times, or patient satisfaction scores. The incidence of moderate pain on injection was higher in the Ampofol group (26%vs. 7% with Diprivan; P < 0.05). Conclusions Ampofol was equipotent to Diprivan with respect to its sedative properties during monitored anesthesia care. Although both groups received pretreatment with intravenous lidocaine, Ampofol was associated with more pain on injection.

Background In addition to local anesthetics, meperidine has been successfully used for local anesthesia. When applied intrathecally, the dorsal horn neurons of the superficial laminae are exposed to high concentrations of meperidine. These cells represent an important point for the transmission of pain information. This study investigated the blocking effects of meperidine on different ionic currents of spinal dorsal horn neurons and, in particular, its impact on the generation of action potentials. Methods Using a combination of the patch clamp technique and the entire soma isolation method, the action of meperidine on voltage-gated Na+ and K+ currents in spinal dorsal horn neurons of rats was described. Current clamp recordings from intact neurons showed the functional relevance of the ion current blockade for the generation of action potentials. Results Externally applied meperidine reversibly blocked voltage-gated Na+ currents with a half-maximum inhibiting concentration (IC50) of 112 microM. During repetitive stimulation, a slight phasic block occurred. In addition, A-type K+ currents and delayed-rectifier K+ currents were affected in a dose-dependent manner, with IC50 values of 102 and 52 microM, respectively. In the current clamp mode, single action potentials were suppressed by meperidine. The firing frequency was lowered to 54% at concentrations (100 microM) insufficient for the suppression of a single action potential. Conclusions Meperidine inhibits the complex mechanism of generating action potentials in spinal dorsal horn neurons by the blockade of voltage-gated Na+ and K+ channels. This can contribute to the local anesthetic effect of meperidine during spinal anesthesia.

Background: Tumescent local anesthesia is a technique for regional anesthesia of the skin and the subcutaneous tissue, using infiltration of large volumes of local anesthetic. The advantages of this technique are (1) simplicity, (2) prolonged postoperative analgesia, (3) low incidence of bleeding, and (4) anesthetization of a large area of the body. There are no reports on the use of tumescent local anesthesia in pediatric patients. Methods: In 30 consecutive pediatric burn patients with American Society of Anesthesiologists physical status class I or II who were 1‐120 months old (34 31.6 months), after induction of anesthesia with nitrous oxide‐ oxygen‐sevoflurane, infiltration with 0.05% (14 ml/kg) or 0.1% (7 ml/kg) lidocaine solution was performed. Anesthesia was maintained with patients spontaneously breathing with 1.5% sevoflurane in nitrous oxide‐ oxygen (50%). The maximum dose of lidocaine used was 7 mg/kg. Postoperative pain was assessed by using the Children’s Hospital of Eastern Ontario Pain Scale (for patients aged up to 5 yr) and by using a visual analog scale (for patients older than 5 yr). A comparison with a historic control group not treated with the tumescent local anesthesia technique was performed. Results: No patients were excluded from the study, and no significant variations in the monitored intraoperative parameters were observed. Five patients had an increase in heart rate and respiratory rate at the beginning of surgery, and of these, two needed a temporary increase in sevoflurane concentration. After the initial incision, no response to painful stimulus was observed. No complications occurred. Six patients required postoperative acetaminophen administration, and 24 patients did not require analgesic treatment. Conclusions: Tumescent local anesthesia with maximum dose of 7 mg/kg lidocaine seems to be safe and the sole possible effective locoregional anesthesia technique for the surgical treatment of noncontiguous pediatric burns. TUMESCENT local anesthesia (TLA) is a technique that provides anesthesia of large areas of skin and subcutaneous tissue by means of the direct infiltration of large volumes of a dilute local anesthetic solution into subcutaneous fat. The injection of such large volumes of fluid produces swelling and firmness (tumescence) of the surgical area. TLA was described for the first time in 1987 by Klein for liposuction. 1 Since then, TLA has been widely studied in awake adults for plastic surgery, general surgery, gynecology, and orthopedics. This technique has been shown to be safe in adult patients regarding lidocaine adsorption and toxicity. 2–7 There are no reports examining the use of TLA in pediatric patients undergoing surgery for the treatment of burns and postburn sequelae. The infiltration of the tumescent local solution may be performed manually (syringe alone or syringe with bag and infusion set) or using a mechanical technique with an infusion pump. 8 The aim of this study was to evaluate the use of the TLA technique in conjunction with general anesthesia for the surgical treatment of burns and postburn sequelae in pediatric patients.

Background A matchstick-sized implanted osmotic pump (Chronogesic) that delivers sufentanil subcutaneously for more than 90 days is being developed to treat chronic pain. This study evaluates pharmacokinetic characteristics related to the absorption of sufentanil using a prototype 60-day system. Methods Twelve opioid-naive volunteers were given naltrexone to prevent opioid effects. Sufentanil, 60 microg, was infused intravenously over 6 h, then 48 h later, the pump was implanted subcutaneously in the upper arm under local anesthesia. Pumps were removed 9 days later. In six volunteers, fever (1.6-3.3 degrees C) was induced with interleukin-2. Plasma was sampled and population pharmacokinetic modeling was performed to estimate in vivo release rate and absorption half-life. Bioavailability was calculated by comparing in vivo to in vitro release rates. The impact of perturbations in release rate on sufentanil plasma concentration (Cp) was simulated. Results Fever had no systematic effect on Cp. Release rate estimated in vivo was similar to that measured in vitro; bioavailability did not differ from 100%. Absorption half-life was 16.2 h. Simulation demonstrated that supplemental release of sufentanil from the implant (as might occur with local heating) increases Cp an average of 2.5-2.8% per hours supplemental dose. Conclusions An implantable osmotic pump delivered sufentanil in vivo at the rate predicted from in vitro experiments. The rate at which sufentanil was absorbed from the subcutaneous space (half-life > 16 h) was markedly slower than reported with subcutaneous or intramuscular administration of large volumes of dilute opioids; this slow absorption dampens potential changes in Cp if release rate is perturbed.

Background Awake tracheal intubation may evoke reflex bronchoconstriction in asthmatics. Whether this effect is altered by the choice of the local anesthetic used or by pretreatment with a beta2-adrenoceptor agonist is unknown. Therefore, we assessed the effect of awake fiberoptic intubation after lidocaine or dyclonine inhalation with or without pretreatment with salbutamol on lung function in asthmatic volunteers. Methods Bronchial hyperreactivity was verified by an inhalational histamine challenge. On four different days in a randomized, double blind fashion the volunteers (n = 10) inhaled either dyclonine or lidocaine with or without salbutamol pretreatment. FEV1 was measured at baseline, following salbutamol or saline inhalation, after lidocaine or dyclonine inhalation, while intubated, and after extubation. Lidocaine and dyclonine plasma concentrations were also measured. Statistics Two-way ANOVA, post hoc tests with Bonferroni correction, results are presented as mean +/- SD. Results Neither lidocaine nor dyclonine inhalation changed FEV1 significantly from baseline compared with placebo inhalation (4.43 +/- 0.67 l vs. 4.29 +/- 0.72 l, and 4.53 +/- 0.63 l vs. 4.24 +/- 0.80 l, respectively). Salbutamol slightly but significantly increased FEV1 (4.45 +/- 0.76 l vs. 4.71 +/- 0.61 l, P = 0.0034, and 4.48 +/- 0.62 l vs. 4.71 +/- 0.61 l, P = 0.0121, respectively). Following awake intubation FEV1 significantly decreased under lidocaine topical anesthesia (4.29 +/- 0.72 l to 2.86 +/- 0.87 l) but decreased even more under dyclonine anesthesia (4.24 +/- 0.80 l to 2.20 +/- 0.67 l; P < 0.0001). While salbutamol pretreatment significantly attenuated the response to intubation, it did not eliminate the difference between the effects of lidocaine and dyclonine. Only minutes after extubation FEV1 was similar compared with baseline. Conclusion In asthmatics, awake fiberoptic intubation evokes a more than 50% decrease in FEV1 following dyclonine inhalation. Using lidocaine for topical anesthesia the decrease in FEV1 is significantly mitigated (35%) and can be even further attenuated by salbutamol pretreatment. Therefore, combined treatment with lidocaine and salbutamol can be recommended for awake intubation while the use of dyclonine, despite its excellent and longer lasting topical anesthesia, may be contraindicated in patients with bronchial hyperreactivity.