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Biomedical subjects

S J Brull

Publications and source records attributed to S J Brull.

At least 19 recordsLinked to original sources

Topical application of acidic bupivacaine to the lumbar ganglion induces mechanical hyperalgesia in the rat.

UNLABELLED: To investigate the neurologic mechanisms of acidic local anesthetic-induced low back pain in humans, we administered bupivacaine and buffered saline at acidic or alkalinized pH at the L5 dorsal root ganglion (DRG) of rats via a hole drilled through the transverse process covering the DRG. Behavioral changes were tested before and after bupivacaine or saline administration. Results indicate that acute single-dose infusion of the DRG with bupivacaine (0.5%) at acidic pH (5.5) induced ipsilateral mechanical hyperalgesia that lasted for 7 days. Acute infusion of alkalinized bupivacaine (pH 7.2), however, caused only minor hyperalgesia that lasted <3 days. Similar results were obtained when bupivacaine was replaced with saline. Alternatively, chronic delivery of acidic saline to the DRG via a subcutaneously implanted osmotic pump resulted in a significant decrease in the withdrawal threshold on the ipsilateral hind paw that lasted for 10 days. In rats receiving chronic treatment of the DRG with alkalinized saline, mechanical hyperalgesia lasted for only 3 days. The results demonstrated that acidic bupivacaine deposited at the DRG causes pain and hyperalgesia when the effects of the local anesthetic have dissipated. These findings may explain the limited therapeutic effects of some acidic local anesthetics used for management of cancer-related and chronic back pain. IMPLICATIONS: Acidic bupivacaine administered at the L5 lumbar ganglion causes pain and hypersensitivity of the hind paw in the rat. These findings may explain the limited therapeutic effects of some acidic local anesthetics used for treatment of cancer-related and chronic back pain.

Administration, Topical↗

Effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents of the dorsal horn neurons in newborn rats.

BACKGROUND: Local anesthetics, such as bupivacaine, have been reported to block calcium currents in primary sensory neurons and to interfere with the release of neurotransmitters in central nervous system neurons. However, it is unknown whether local anesthetics affect the calcium current activity of central nervous system neurons. METHODS: Using a traditional whole cell voltage clamp technique, effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents (HVA-Ic(a)) were investigated in enzymatically dissociated dorsal horn neurons of neonatal rats. Calcium currents were evoked by testing pulses from a holding potential of -90 to 0 mV. RESULTS: Bupivacaine significantly reduced HVA-Ic(a) in a dose-dependent manner. The peak HVA-Ic(a) decreased by 24.5+/-2.5, 32.0+/-6.8, 59.4+/-6.2, 88.3+/-1.5, and 91.6+/-1.1% in response to 10, 30, 50, 100 and 200 microM bupivacaine, respectively. Unlike bupivacaine, ropivacaine markedly increased HVA-Ic(a) at lower concentrations (< 50 microM) but decreased HVA-Ic(a) at higher concentrations (> or = 50 microM). The percent increases in peak HVA-Ic(a) induced by 10 and 30 microM ropivacaine were 95+/-19.1 and 41.6+/-8.3%, respectively. The percent decreases in response to 50, 100, and 200 microM ropivacaine were 21.1+/-2.1, 63.2+/-6.0 and 79.1+/-7.6%, respectively. Results indicate that the inhibitory potency of ropivacaine on HVA-Ic(a) was significantly lower than that of bupivacaine at the same concentrations. CONCLUSIONS: The current study showed that bupivacaine inhibited HVA-Ic(a) recorded from dorsal horn neurons and that ropivacaine increased HVA-Ic(a) at lower concentrations but decreased HVA-Ic(a) at higher concentrations. The inhibitory potency of ropivacaine was lower than that of bupivacaine. Inhibition of calcium currents of central nervous system neurons may be related to the systemic neurotoxic effects of local anesthetics (e.g., convulsions, seizures).

Amides↗

Perfusion of the mechanically compressed lumbar ganglion with lidocaine reduces mechanical hyperalgesia and allodynia in the rat.

The rat L(5) dorsal root ganglion (DRG) was chronically compressed by inserting a hollow perforated rod into the intervertebral foramen. The DRG was constantly perfused through the hollow rod with either lidocaine or normal saline delivered by a subcutaneous osmotic pump. Behavioral evidence for neuropathic pain after DRG compression involved measuring the incidence of hindlimb withdrawals to both punctate indentations of the hind paw with mechanical probes exerting different bending forces (hyperalgesia) and to light stroking of the hind paw with a cotton wisp (tactile allodynia). Behavioral results showed that for saline-treated control rats: the withdrawal thresholds for the ipsilateral and contralateral paws to mechanical stimuli decreased significantly after surgery and the incidence of foot withdrawal to light stroking significantly increased on both ipsilateral and contralateral hind paws. Local perfusion of the compressed DRG with 2% lidocaine for 7 days at a low flow-rate (1 microl/h), or for 1 day at a high flow-rate (8 microl/h) partially reduced the decrease in the withdrawal thresholds on the ipsilateral foot but did not affect the contralateral foot. The incidence of foot withdrawal in response to light stroking with a cotton wisp decreased significantly on the ipsilateral foot and was completely abolished on the contralateral foot in the lidocaine treatment groups. This study demonstrated that compression of the L(5) DRG induced a central pain syndrome that included bilateral mechanical hyperalgesia and tactile allodynia. Results also suggest that a lidocaine block, or a reduction in abnormal activity from the compressed ganglia to the spinal cord, could partially reduce mechanical hyperalgesia and tactile allodynia.

Anesthetics, Local↗

Enhancement of experimental pruritus and mechanically evoked dysesthesiae with local anesthesia.

Pain reduces itch-a commonly known effect of scratching the skin. Experimentally produced itch from histamine is sometimes accompanied by secondary sensations of pain. The present study investigated the effects of eliminating this pain, by means of a local anesthetic, on the itch and the enhanced mechanically evoked itch and pain that occur after an intradermal injection of histamine. In ten human subjects, the volar forearm was injected with either 20 microl of 2% chloroprocaine (experimental arm), or 20 microl of saline (control arm). Histamine 10 microl was injected into each bleb, and the resulting magnitude of itch estimated. The borders of three cutaneous areas were mapped within which mechanical stimulation of the skin surrounding the bleb elicited abnormal sensations (dysesthesiae): alloknesis, defined as itch evoked by innocuous stroking, and hyperalgesia and hyperknesis, characterized, respectively, by enhanced pain and enhanced itch evoked by pricking the skin with a fine tipped filament. The magnitude and duration of itch were significantly greater and the areas of dysesthesia significantly larger for the experimental than for the control arm. It is hypothesized that there exist two classes of histamine-sensitive primary afferent neurons. One class is "pruritic", and mediates itch whereas the other is "antipruritic", and evokes a centrally mediated reduction in histamine-evoked itch and dysesthesiae. It is further suggested that the anesthetic blocked the discharges of the antipruritic afferents, preventing the central inhibition from occurring and thereby unmasking the effects of the pruritic afferents.

Adult↗

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.

Adult↗

The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery.

UNLABELLED: Patients undergoing vascular surgery have a high risk of suffering major postoperative cardiac events. Preoperative myocardial ischemia as detected by Holter monitoring identifies a high-risk subgroup whose postoperative ischemia, similarly detected, seems to herald major cardiac events. In this study, we determined whether systematic, patient-specific postoperative heart rate control with beta-adrenergic blocker therapy decreases the incidence of postoperative ischemia among high-risk vascular surgery patients. A total of 26 of 150 patients who underwent elective vascular surgery and were monitored preoperatively by 24-h Holter were found to have significant myocardial ischemia as defined by ST-segment depression. The minimal heart rate at which this ST-segment depression occurred was identified (ischemic threshold), and these 26 patients were then randomized to receive continuous i.v. beta-blockade with esmolol or placebo plus usual medical therapy, aiming to reduce the postoperative heart rate to 20% below the ischemic threshold. All patients were monitored by Holter for 48 h postoperatively. Postoperative Holter readings were analyzed for the incidence of ischemia and for the number of hours during which heart rate was controlled below the ischemia threshold. Patients had a median of two episodes of preoperative ischemia lasting a median of 30 min (range 1-155 min). A total of 15 patients were randomized to receive esmolol, and 11 were randomized to receive placebo. The two groups were comparable with respect to clinical characteristics and incidence and duration of preoperative ischemia. Ischemia persisted in the postoperative period in 8 of 11 placebo patients (73%), but only 5 of 15 esmolol patients (33%) (P < 0.05). Of the 15 esmolol patients, 9 had mean heart rates below the ischemic threshold, and all 9 had no postoperative ischemia. A total of 4 of 11 placebo patients had mean heart rates below the ischemic threshold, and 3 of the 4 had no postoperative ischemia. There were two postoperative cardiac events among patients who had postoperative ischemia (one placebo, one esmolol) and whose mean heart rates exceeded the ischemic threshold. Our data suggest that patient-specific, strict heart rate control aiming for a predefined target based on individual preoperative ischemic threshold was associated with a significant reduction and frequent elimination of postoperative myocardial ischemia among high-risk patients and provide a rationale for a larger trial to examine this strategy's effect on cardiac risk. IMPLICATIONS: Patients who undergo peripheral vascular surgery often experience transient cardiac complications and/or permanent heart damage just after surgery because of inadequate myocardial blood flow. In this study, we identified patients at high risk of cardiac complications after vascular surgery and showed that if their heart rate was carefully controlled for 48 h after surgery, myocardial ischemia, a common marker of heart injury, was markedly reduced.

Adrenergic beta-Antagonists↗

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.

Adult↗

Electromyographic assessment of ulnar nerve motor block induced by lidocaine.

STUDY OBJECTIVE: To determine the differences in the onset time and duration of motor block produced by lidocaine 1% and lidocaine 2% via a quantitative and objective method, the measurement of compound muscle action potentials (CMAPs). STUDY DESIGN: Prospective study. SETTING: Main operating rooms of a university hospital. PATIENTS: 20 consecutive patients undergoing surgery not requiring intraoperative muscle relaxation. INTERVENTIONS: General anesthesia with unilateral ulnar nerve block was administered. In patients' nondominant (experimental) arms, an insulated block needle was placed adjacent to the ulnar nerve at the wrist while continuous nerve stimulation was delivered to ensure its proper placement. Through this needle, lidocaine 1% or lidocaine 2% was injected. The dominant (control) arm received no injection. MEASUREMENTS AND MAIN RESULTS: Monitoring of ulnar nerve-evoked CMAPs was performed simultaneously on both arms. Ulnar nerve function was assessed at baseline and then at 10-second intervals by automatically measuring the amplitude of the evoked CMAPs on a two-channel electromyogram. The mean (+/- SEM) baseline CMAP amplitude prior to injection of lidocaine 1% was 3.10 +/- 0.87 mV and 3.06 +/- 0.89 mV for the experimental and control ulnar nerves, respectively (p = NS); for lidocaine 2%, baseline CMAP amplitude was 3.58 +/- 1.39 mV and 3.70 +/- 1.46 mV, respectively (p = NS). Over the course of the study, the control CMAP amplitude varied by < 12%. At the experimental ulnar nerve, 90% CMAP decrease after injection of lidocaine 1% and lidocaine 2% occurred 7.5 +/- 2 minutes and 5 +/- 1.5 minutes, respectively (p = NS), whereas maximal blockade was achieved after 15 +/- 3 minutes and 11 +/- 5 minutes, respectively (p = NS). Recovery of CMAP to 90% of baseline occurred 184 +/- 31 minutes after injection of lidocaine 1% and 248 +/- 30 minutes following lidocaine 2% (p = NS). CONCLUSION: The present study describes a technique that can be used in vivo to objectively measure the speed of onset and duration of local anesthetic-induced motor blockade. Although statistically not different, lidocaine 2% demonstrated a faster onset and longer duration of ulnar nerve motor block than lidocaine 1%.

Action Potentials↗

The use of relational databases in the transition from quality assurance to continuous quality improvement: a clinical practice model.

The use of both clinical medical and administrative databases is discussed in the context of an academic anesthesiology's transition from the tenets of quality assurance to those of continuous quality improvements. A historical framework is presented. The basic and aggregate models are introduced, and examples are used to illustrate the composite system.

Anesthesiology↗

Comparative recovery of 50-Hz and 100-Hz posttetanic twitch following profound neuromuscular block.

STUDY OBJECTIVE: To determine if posttetanic twitch following 100-Hz tetanic stimulation enables titration of a nondepolarizing relaxant infusion to a greater depth of block than that achieved with posttetanic twitch following 50 Hz. STUDY DESIGN: Prospective, observational study. SETTING: Operating rooms of a university tertiary care center. PATIENTS: 10 ASA physical status II and III patients free of known neuromuscular disease and undergoing general endotracheal anesthesia for routine elective surgery. INTERVENTIONS: Following induction of general anesthesia, neuromuscular block was maintained with a continuous intravenous vecuronium infusion. Depth of neuromuscular block was assessed by tactile evaluation of the evoked responses of the adductor pollicis muscle following supramaximal stimulation of the ulnar nerve via surface electrodes. The vecuronium infusion was titrated to loss of posttetanic twitch following 100-Hz tetanic stimulation, at which point the infusion was discontinued. MEASUREMENTS AND MAIN RESULTS: 100-Hz tetanic stimulation was repeated every two minutes until recovery of the first posttetanic twitch, at which point 50-Hz tetanic stimulation was repeated every two minutes until recovery of the first posttetanic twitch. The median time (interquartile range) from discontinuation of the vecuronium infusion to recovery of the first posttetanic twitch following 100-Hz tetanic stimulation was 27% faster than the corresponding time to recovery of the first posttetanic twitch following 50-Hz tetanic stimulation [19 (10 to 24) min and 26 (20 to 30) min respectively, p < 0.002]. CONCLUSIONS: Posttetanic twitch following 100-Hz tetanic stimulation enables titration of a vecuronium infusion to a greater depth of block than posttetanic twitch following 50-Hz tetanic stimulation. The present findings should enable more effective titration of this relaxant, thereby reducing the likelihood of unwanted patient movement or unduly prolonged recovery due to relaxant overdosing.

Adult↗

The effect of solubility and hyperlipidemia on perioperative arterial blood gas tensions.

A case is presented to illustrate the need for technical care when handling blood gas samples. The physics of solubility are used to show hour samples changed their oxygen tension (pO2) during handling, while investigating a clinical case to show the effect of hyperlipidemia on blood gases. It appeared that inadvertent access to air allowed atmospheric oxygen to equilibrate with the sample. The physical laws predicting the effect of partial pressure and temperature on gas solubility in a liquid are illustrated by the pO2 levels measured in this case. Effects due to hyperlipidemia were not observed. The calculations are described in detail. Brief suggestions for sample handling to avoid misleading results from such cases are discussed.

Blood Gas Analysis↗

The effect of intravenous ketorolac given intraoperatively versus postoperatively on outcome from gynecologic abdominal surgery.

STUDY OBJECTIVES: To examine the effect of timing of an intravenous (i.v.) dose (intraoperative vs. postoperative) of ketorolac tromethamine on pain scores and overall outcome after total abdominal hysterectomy (TAH) and myomectomy. DESIGN: Prospective, randomized, placebo-controlled study. PATIENTS: 248 ASA physical status I and II adult female patients scheduled for elective hysterectomy or myomectomy. INTERVENTIONS: General anesthesia was administered that consisted of thiopental sodium for induction, enflurane or isoflurane in nitrous oxide-oxygen for maintenance, and small doses of fentanyl and midazolam. Patients were randomized into three groups to receive toradol/placebo on a dosing schedule of dose 1 given one-half hour prior to expected end of surgery, dose 2 given on awakening in the postanesthesia care unit, and doses 3, 4, and 5 given at 6, 12, and 18 hours, respectively, after dose 2; Group 1 patients received placebo (saline) for dose 1, ketorolac 60 mg i.v. for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 2 patients received ketorolac 60 mg i.v. for dose 1, placebo for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 3 patients received placebo for all doses. All patients were given i.v. morphine PCA postoperatively, and morphine usages, visual analog pain intensity (VAS) scores, as well as adverse events and median times to recovery milestones were recorded. MEASUREMENTS AND MAIN RESULTS: VAS scores (mean) before dose 2 were significantly lower in Group 2 than Group 1, as were at-rest evaluations at 15 minutes and one hour. Group 2 patients also had decreased morphine requirements as compared to placebo. Both ketorolac groups (Groups 1 and 2) had significantly higher values for patient and observer overall ratings, case of nursing care, and tolerability as compared to placebo (Group 3). There were no significant differences among groups in adverse events or median times to recovery milestones. CONCLUSIONS: Although it is possible to demonstrate an improvement in early postoperative pain scores with intraoperative ketorolac and better overall ratings of ketorolac both intraoperatively and postoperatively as compared with placebo, the lack of clinically significant differences in analgesic efficacy in the two active study groups indicates the need for a careful consideration by the clinician of the risks versus benefits involved in the administration of antiplatelet medication in the perioperative period.

Adult↗

Patient awareness during general anesthesia: a shocking outcome.

Patient awareness under minimal anesthesia may include the painful impulses of a nerve stimulator used for the monitoring of muscle relaxation. We present a case where discomfort from nerve stimulation was greater than that caused by the surgical incision or the endotracheal tube.

Abscess↗

The effect of intradermal administration of lidocaine and morphine on the response to thermal stimulation.

Opioids appear to exert a peripheral effect by gaining access to peripheral opioid receptors. It has been proposed that inflammatory processes and highly osmotic substances could alter the perineural barrier, thereby allowing easy access to opioid receptors. Although local anesthetics do not have osmotic activity, they are highly active on neural tissue and appear to work synergistically with opioids when administered for major conduction blockade. We therefore evaluated, in a double-blind fashion, the combination of lidocaine plus morphine in an attempt to provide a scientific basis for the use of a combination of morphine plus local anesthetics in the periphery. Seven thermal stimuli in 2 degrees C increments (range 40-52 degrees C) were delivered in a random sequence by a computer-controlled thermistor to one of three pretreated sites on 10 volunteers' forearms: reference site (no injection), lidocaine site (0.1-mL intradermal injection of lidocaine 0.5%), or lidocaine plus morphine site (0.1 mL of 0.5 mg of morphine plus lidocaine 1%). Pain responses to the thermal stimuli were rated by the volunteers using the method of magnitude estimation. Pain scores indicated that the combination of lidocaine plus morphine was not more effective than lidocaine alone in attenuating the heat-induced pain. Twenty and 120 min after injection, scores at the lidocaine plus morphine site were 37% and 20% greater than those at the lidocaine site. The addition of morphine to lidocaine did not result in an improvement in the analgesic efficacy and actually had an antianalgesic effect.

Adult↗