bluuebunny/crossref_metadata_2025 huggingface dataset:
Local Anesthetic Test Dose as a Predictor of Effective Epidural Opioid Analgesia
Authors: Weitz Sandra R. , Drasner Kenneth
Published: November 2003

Background

When local anesthetic is used to produce epidural anesthesia intraoperatively, epidural catheter placement is confirmed. However, when epidural catheters are placed intraoperatively only to provide postoperative opioid analgesia, correct catheter placement may not be confirmed by administration of a local anesthetic. The current study tests the hypothesis that the extent of sensory blockade produced by a 10-ml dose of 1.5% lidocaine can be used to predict the adequacy of epidural opioid analgesia.

Methods

Forty-nine patients undergoing major abdominal surgery in whom a lumbar epidural catheter was placed intraoperatively were studied, but no more than 3 ml 1% lidocaine had been injected. Placement of the epidural catheter was assessed in the postanesthesia care unit by administration of a 10-ml dose of 1.5% lidocaine. The extent of sensory blockade was determined using the pinprick technique: All dermatomes, T2 and below, were assessed and scored using 1 point per dermatome per side from L1 to T2 to a maximum of 24 points. Scores were arbitrarily divided into three groups, where group 1, 0-7 points; group 2, 8-15 points; and group 3, 16-24 points. Epidural morphine infusion was initiated independently of the extent of the sensory blockade and adjusted using predetermined guidelines. Adequacy of opioid-induced analgesia was determined using the visual analog scale.

Results

Significantly lower visual analog scale scores for pain at rest and with movement from epidural morphine infusion were associated with sensory blockade score of 16-24 points. Seven patients failed to obtain a detectable sensory block. No patient requested alternative analgesia. None of the epidural catheters was removed because of inadequate pain relief, even in patients who failed to obtain a detectable sensory block.

Conclusions

Extensive sensory block from 10 ml 1.5% lidocaine was associated with excellent epidural opioid analgesia. Extent of analgesia after a 10-ml test dose of 1.5% lidocaine can be used to predict the adequacy of analgesia resulting from an epidural opioid infusion. The failure of a local anesthetic dose to produce sensory blockade does not necessarily predict a failure to produce analgesia from an epidural opioid infusion, as indicated by the presence of analgesia in several patients without detectable sensory block.
Automated Echocardiographic Analysis
Authors: Perrino Albert C. Jr. MD , Luther Martha A. , O'Connor Theresa Z. , Cohen Ira S.
Published: November 2003

Background

Although transesophageal echocardiography allows continuous intraoperative cardiac monitoring, the technique has been limited by the lack of a method for realtime, quantitative assessment of cardiac chamber size and systolic function. Automated border detection (ABD), based on an analysis of integrated backscatter, is a new technique that is purported to provide real-time, quantitative assessment of left ventricular (LV) areas and fractional area change (FAC). A prospective investigation was designed to assess the accuracy and trending capability of ABD during continuous intraoperative monitoring.

Methods

In 16 patients monitored throughout noncardiac surgical procedures, serial real-time estimates of LV end-diastolic area (EDA), end-systolic area (ESA), and FAC by ABD were compared with paired off-line manual measurements made by two experiences echocardiographers.

Results

There was a high correlation between real-time ABD estimates of LV ESA (r = 0.93), EDA (r = 0.89), and FAC (r = 0.90) to those of the off-line technique. The automated technique systematically underestimated both EDA and ESA, resulting in a small underestimation of FAC. The automated technique demonstrated an accuracy rate of 96% in tracking serial changes in LV area. The technique performed with an 83% sensitivity and 85% specificity for detecting acute changes in LV area.

Conclusions

This analysis of serial intraoperative echocardiograms demonstrates the accuracy of ABD to estimate LV area in real time and to track serial changes in cardiac area during surgery. Although ABD is an automated technique, application by personnel experienced in its operation and an echocardiographic system that includes lateral-gain adjustment controls are recommended for its optimal performance.
Placental Transfer and Neonatal Effects of Epidural Sufentanil and Fentanyl Administered with Bupivacaine during Labor
Authors: Loftus John R. , Hill Harlan , Cohen Sheila E.
Published: November 2003

Background

This randomized double-blind investigation was designed to study the placental transfer and neonatal effects of epidural sufentanil and fentanyl infused with bupivacaine for labor analgesia.

Methods

Healthy parturient women (n = 36) received epidural bupivacaine alone (group B) or with fentanyl (group B-F) or sufentanil (group B-S). Group B received a 12-ml bolus of 0.25% bupivacaine followed by a 10 ml/h infusion of 0.125% bupivacaine. Groups B-F and B-S received a 12-ml bolus of 0.125% bupivacaine with 75 micrograms fentanyl or 15 micrograms sufentanil, respectively, followed by 10 ml/h of 0.125% bupivacaine with fentanyl 1.5 micrograms/ml or sufentanil 0.25 micrograms/ml. Maternal venous (MV) and umbilical arterial (UA) and umbilical venous (UV) bupivacaine and opioid plasma concentrations were determined. Neonatal assessment included Apgar scores, umbilical cord blood gas analyses, and neurobehavioral testing at delivery and at 2 and 24 h of life using the Neurologic and Adaptive Capacity Score (NACS).

Results

The mean total dose of fentanyl was 136.6 +/- 13.1 micrograms (SEM), and of sufentanil, 23.8 +/- 1.8 micrograms. Although administered in a ratio of 5.7:1, fentanyl and sufentanil MV plasma concentrations were in the ratio of 27:1. UV/MV ratios were 0.37 for fentanyl and 0.81 for sufentanil. Fentanyl was detected in most UA samples, whereas sufentanil was present in only one sample. Neonatal condition was good and generally similar in all groups, with the exception of a lower NACS at 24 h in group B-F.

Conclusions

Although the degree of placental transfer of sufentanil appeared greater than that of fentanyl, lower MV sufentanil concentrations resulted in less fetal exposure to sufentanil. The lower NACS at 24 h in group B-F may reflect the continued presence of fentanyl in the neonate.
Binding of Halothane to Serum Albumin Demonstrated Using Tryptophan Fluorescence
Authors: Johansson Jonas S. , Eckenhoff Roderic G. , Dutton P. Leslie
Published: November 2003

Background

The site of action of general anesthesia remains controversial, but evidence in favor of specific protein target(s) is accumulating. Saturable binding of halothane to bovine serum albumin (BSA) has recently been reported using photoaffinity labeling and fluorine 19 nuclear magnetic resonance spectroscopy. We report a new approach to study anesthetic binding to soluble proteins, based on native tryptophan fluorescence.

Methods

Thymol-free halothane and fatty acid-free BSA were equilibrated in gas-tight Hamilton syringes and dispensed into stoppered quartz cuvettes at predetermined dilutions. Steady-state fluorescence spectroscopy was used to study their interaction.

Results

Halothane quenched the tryptophan fluorescence of BSA in a concentration-dependent, saturable manner with a dissociation constant = 1.8 +/- 0.2 mM and a Hill number = 1.0 +/- 0.1. The two optical isomers of halothane bound to BSA with equal affinity. The ability of halothane to quench BSA tryptophan fluorescence was markedly decreased at pH 3.0 (which causes full uncoiling of BSA), with loss of saturable binding. Diethyl ether displaced a portion of halothane from its binding sites. Circular dichroism spectroscopy revealed no significant effect of halothane or diethyl ether on the secondary structure of BSA.

Conclusions

The results suggest that halothane binds in hydrophobic domains containing tryptophan in BSA. This approach may prove useful for studying the interaction of volatile anesthetics and proteins and has the advantage that the location of halothane in the protein is identified.
Interaction of Halothane with Inhibitory G-proteins in the Human Myocardium
Authors: Schmidt Ulrich , Schwinger Robert H. G. , Bohm Michael
Published: November 2003

Background

Halothane has been reported to possess a catecholamine-sensitizing effect in laboratory animals and in anesthetized patients and to enhance the positive inotropic effect of isoproterenol in human papillary muscle strips. The current study was designed to investigate further the underlying subcellular mechanisms on human myocardium, in particular the mechanism of action of halothane on G-proteins.

Methods

To investigate the effect of halothane on adenylyl cyclase activity, isoproterenol-, guanylylimidodiphosphate (Gpp(NH)p)-, and forskolin-activated enzyme activities were studied alone and in the presence of halothane in native and manganese-treated membranes. The mechanisms of halothane interaction with inhibitory G-proteins (G1) were studied in adenosine diphosphate-ribosylation studies with pertussis toxin and immunochemical techniques.

Results

Halothane (1%) augmented isoproterenol- and Gpp(NH)p-stimulated adenylyl cyclase activity but had no effect on forskolin-stimulated enzyme activity. Manganese ions inhibited the stimulating effect of isoproterenol and Gpp(NH)p on adenylyl cyclase activity, but the effect of forskolin remained unchanged in control and halothane-treated membranes. In the presence of pertussis toxin, the effect of isoproterenol and Gpp(NH)p on adenylyl cyclase activity was enhanced, but further stimulation by halothane was abolished. Halothane did not influence the attachment of Gi alpha to the membrane. No effect of halothane on adenosine diphosphate-ribosylation of Gi alpha by pertussis toxin was observed.

Conclusions

Halothane stimulates adenylyl cyclase activity by inhibiting the function of the inhibitory G-proteins by interfering with the effects of the alpha subunits or beta gamma subunits with the effector. Decreased membrane attachment of Gi alpha in the presence of halothane does not occur. The interaction of alpha and beta gamma subunits is not affected by halothane. Halothane does not impair the binding of pertussis toxin to the Gi alpha-protein.
Inhibitory Effect of Lidocaine on Cultured Porcine Aortic Endothelial Cell-dependent Antiaggregation of Platelets
Authors: Az-ma Toshiharu , Hardian MD , Yuge Osafumi
Published: November 2003

Background

Vascular spasm is a well-known complication during vascular surgery. Topical lidocaine is frequently used to prevent this spasm. However, the effects of lidocaine on the endothelium-dependent antiaggregation are not clear.

Methods

The aggregation of platelet-rich plasma (PRP) obtained from healthy volunteers was measured by the turbidimetric technique at 37 degrees C. (1) Cultured porcine aortic endothelial cells were preincubated with lidocaine (3.7 microM to 37 mM), NG-methyl-L-arginine (300 microM), or indomethacin (10 microM) for 30 min. The preincubation medium was exchanged with a medium containing +/- 1 microM bradykinin for 1-min stimulation of endothelial cells. One hundred microliters of the supernatant was then added to PRP (750 micro1) just after stimulation of PRP with collagen (4 micrograms/ml). (2) Authentic nitric oxide (NO) or prostacyclin (PGI2) was applied to collagen-stimulated PRP with or without lidocaine (100 micrograms/ml).

Results

(1) The supernatant from endothelial cells without bradykinin stimulation showed "basal" antiaggregation (13.8 +/- 3.2%; n = 6). Bradykinin enhanced the antiaggregation (100 +/- 0%; n = 6). NG-methyl-L-arginine or indomethacin (antagonists of NO or PGI2) inhibited the bradykinin-evoked antiaggregation (10.3 +/- 2.1% and 13.6 +/- 3.7%, respectively; n = 6). Simultaneous preincubation of both agents completely blocked the effect (-4.2 +/- 2.8%; n = 6). Lidocaine failed to influence basal antiaggregation, but it inhibited bradykinin-stimulated antiaggregation in a concentration-dependent manner (concentration causing 50% inhibition = 108 +/- 41 microM; n = 6). (2) In contrast, lidocaine did not shift the 50% effective concentration of NO (control, 1.3 +/- 0.1 microM vs. lidocaine, 1.6 +/- 0.1 microM) or PGI2 (control, 405 +/- 54 nM vs. lidocaine, 257 +/- 41 nM) for antiaggregation.

Conclusions

Our results suggest that lidocaine has an inhibitory effect on antiaggregation derived from endothelial cells, caused by the inhibition of NO and PGI2 released from endothelial cells.
Halothane Selectively Inhibits Bradykinin-induced Synovial Plasma Extravasation
Authors: Pierce Pamela A. , King Bryan S. , Rampil Ira J. , Levine Jon D.
Published: November 2003

Background

In vitro studies demonstrate that halothane, but not isoflurane, inhibits bradykinin-induced calcium currents and prostacyclin release in cultured endothelial cells. Because bradykinin is an important endogenous mediator of inflammation, we assessed the effects of halothane, isoflurane, and pentobarbital on plasma extravasation, a component of tissue inflammation induced by bradykinin, in rats.

Methods

We anesthetized 23 rats with halothane (0.8 or 1.3 minimum alveolar concentration [MAC]), isoflurane (1.3 MAC), or pentobarbital (total of 85 mg/kg intraperitoneally). Their tracheas were intubated and their lungs mechanically ventilated. After intravenous administration of Evans blue dye, we perfused normal saline followed by bradykinin or platelet-activating factor, another inflammatory mediator, intraarticularly via needles placed in the knee joint. We collected perfusate and estimated extravasation by measuring dye in the perfusate using spectrophotometry.

Results

Bradykinin increased plasma extravasation eight- to ninefold above baseline in both pentobarbital- and isoflurane-anesthetized rats. In contrast, bradykinin-induced plasma extravasation at 0.8 MAC and 1.3 MAC of halothane was approximately 40% (P < 0.01) and 15% (P < 0.001), respectively, of that in pentobarbital- and isoflurane-anesthetized rats. Baseline plasma extravasation was lower in rats anesthetized with either concentration of halothane compared with pentobarbital or isoflurane (all P < 0.001). Platelet-activating factor-induced plasma extravasation was similar for all anesthetics.

Conclusion

Halothane, but not isoflurane or pentobarbital, inhibits both baseline and bradykinin-induced peripheral plasma extravasation, demonstrating that volatile anesthetics differentially modulate this important component of inflammation.
Relation between Functional Deficit and Intraneural Local Anesthetic during Peripheral Nerve Block
Authors: Popitz-Bergez F. A. , Leeson S. , Strichartz G. R. , Thalhammer J. G.
Published: November 2003

Background

During peripheral nerve block, local anesthetic (LA) penetrates within and along the nerve to produce the observed functional deficits. Although much is known about the kinetics and steady-state relation for LA inhibition of impulse activity in vitro in isolated nerve, little is known about the relation between functional loss and intraneural LA content in vivo. This study was undertaken to investigate the relation of functional change to intraneural LA.

Methods

A sciatic nerve block was performed in rats with 0.1 ml 1% lidocaine radiolabeled with 14C. The total intraneural uptake of LA was determined at different times after injection, and the distribution of lidocaine along the nerve was assayed at different stages of functional block. Drug content was also compared with equilibrium lidocaine uptake in the isolated rat sciatic nerve.

Results

Total intraneural lidocaine in vivo increased to near steady-state in about 3 min, stabilizing at approximately 14.3 nmol/mg wet tissue for about 12 min before decreasing to zero at 70 min after injection. Although intraneural lidocaine was 1.6% of the injected dose during full block, only 0.3% was left when deep pain sensation returned and 0.065% was still detected when functions fully recovered. Despite these large differences in total lidocaine content, the longitudinal distribution remained constant. Intraneural lidocaine concentrations obtained at full block and partial recovery could be achieved in vitro by equilibration in 0.7-0.9 and 0.2-0.3 mM lidocaine, respectively.

Conclusions

During peripheral nerve block only a small amount of injected LA penetrates into the nerve. The intraneural content of LA correlates with the depth of functional block.
Isoflurane's Enhancement of Chloride Flux through Rat Brain γ-Aminobutyric Acid Type A Receptors Is Stereoselective
Authors: Quinlan Joseph J. , Firestone Susan , Firestone Leonard L.
Published: November 2003

Background

Recent evidence is consistent with the view that volatile anesthetics interact directly with excitable membrane-bound channel proteins. If these agents interact directly with chiral centers in the neuronal cell membrane, then their effects should be stereoselective. Using rat brain membranes enriched in gamma-aminobutyric acid type A (GABAA) receptors, we investigated the hypothesis that the permeability response of this well-characterized central nervous system channel protein to stereoisomers of isoflurane is stereoselective.

Methods

Rat brain synaptic microvesicles were prepared by differential centrifugation. Agonist-stimulated 36Cl- flux through membrane-bound GABAA receptors was assayed in the presence of (+)- and (-)-isoflurane and compared with control conditions.

Results

Both isomers increased the potency and efficacy of GABA; however, (+)-isoflurane was significantly more potent and efficacious than the (-)-isomer. For example, the (+)-isomer (140 microM) reduced the median effective concentration of GABA from 12.7 +/- 1.0 to 5.4 +/- 0.5 microM, whereas the (-)-isomer reduced it to 9.6 +/- 1.0 microM (P < 0.001). The (+)-isomer also was 1.6 times as potent as the (-)-isomer in augmenting 5 microM GABA-gated flux (79 +/- 11 vs. 130 +/- 17 microM, respectively; P = 0.01). In addition, the (+)-isomer produced significantly greater maximal enhancement of flux (9.4 +/- 0.4 vs. 7.0 +/- 0.3 nmol.mg-1.3 s-1; P < 0.001).

Conclusions

Isoflurane's effects on GABA-gated chloride flux were stereoselective. This result supports direct interaction with a stereoselective site, possibly the GABAA channel protein itself, rather than a nonspecific perturbation of the surrounding membrane lipid. In addition, these findings, from a functional assay using mammalian brain, agree with recent observations in invertebrate ion channels and mammalian neuronal cell cultures.
Heat Flow and Distribution during Epidural Anesthesia
Authors: Matsukawa Takashi , Sessler Daniel I. , Christensen Richard , Ozaki Makoto , Schroeder Marc
Published: November 2003

Background

Core hypothermia after induction of epidural anesthesia results from both an internal core-to-peripheral redistribution of body heat and a net loss of heat to the environment. However, the relative contributions of each mechanism remain unknown. The authors thus evaluated regional body heat content and the extent to which core hypothermia after induction of anesthesia resulted from altered heat balance and internal heat redistribution.
Role of the Vagus Nerve in the Antidysrhythmic Effect of Dexmedetomidine on Halothane/Epinephrine Dysrhythmias in Dogs
Authors: Kamibayashi Takahiko , Hayashi Yukio , Mammoto Tadanori , Yamatodani Atsushi , Sumikawa Koji , Yoshiya Ikuto
Published: November 2003

Background

Dexmedetomidine, an alpha2-adrenergic agonist, can prevent the genesis of halothane/epinephrine dysrhythmias through the central nervous system. Because stimulation of alpha2adrenoceptors in the central nervous system enhances vagal neural activity and vagal stimulation is known to inhibit digitalis-induced dysrhythmias, dexmedetomidine may exert the antidysrhythmic property through vagal stimulation. To address this hypothesis, the effect of dexmedetomidine in vagotomized dogs was examined and compared with that in intact dogs. In addition, the effect of vagotomy on the antidysrhythmic action of doxazosin, an alpha1antagonist, was studied.
Acute Pain Management
Authors: Warfield Carol A. , Kahn Cynthia H.
Published: November 2003

Background

The objective of the survey was to assess the status of acute pain management in U.S. hospitals and attitudes of adults in the U.S. toward postoperative pain management, information that has not been previously available.
Where Are the Costs in Perioperative Care?: Analysis of Hospital Costs and Charges for Inpatient Surgical Care
Authors: Macario Alex , Vitez Terry S. , Dunn Brian , McDonald Tom
Published: November 2003

Background

Many health-care institutions are emphasizing cost reduction programs as a primary tool for managing profitability. The goal of this study was to elucidate the proportion of anesthesia costs relative to perioperative costs as determined by charges and actual costs.
Shivering Threshold during Spinal Anesthesia Is Reduced in Elderly Patients
Authors: Vassilieff Nicolas , Rosencher Nadia , Sessler Daniel I. , Conseiller Christian
Published: November 2003

Background

Both accidental and perioperative hypothermia are common in the elderly. The elderly are at risk because their responses to hypothermia may be delayed or less efficient than in those of younger subjects. For example, the vasoconstriction threshold during isoflurane anesthesia is [nearly equal] 1 degree Celsius less in elderly than younger patients. However, the extent to which other cold defenses are impaired in the elderly remains unclear, especially in those older than 80 yr. Operations suitable for spinal anesthesia provided an opportunity to quantify shivering thresholds in patients of varying ages. Accordingly, the hypothesis that the shivering threshold is reduced as a function of age during spinal anesthesia was tested.
Effects of Storage Time on Quantitative and Qualitative Platelet Function after Transfusion
Authors: Rosenfeld Brian A. , Herfel Barbara , Faraday Nauder , Fuller Alice , Braine Hayden
Published: November 2003

Background

Platelet transfusions are being used increasingly in patients with thrombocytopenia to improve hemostatic function before surgery and invasive procedures. However, there are limited data on the immediate quantitative and qualitative platelet response after transfusion. Some authors have suggested that transfused platelets require time in vivo to regain maximal function, which is dependent on the duration of platelet storage. Therefore, the timing of surgery and invasive procedures with optimal platelet function may not be occurring.
Visual Display Format Affects the Ability of Anesthesiologists to Detect Acute Physiologic Changes: A Laboratory Study Employing a Clinical Display Simulator
Authors: Gurushanthaiah Keerti , Weinger Matthew B. , Englund Carl E.
Published: November 2003

Background

Anesthesiologists use data presented on visual displays to monitor patients' physiologic status. Although studies in nonmedical fields have suggested differential effects on performance among display formats, few studies have examined the effect of display format on anesthesiologist monitoring performance.
Linearity of Pharmacokinetics and Model Estimation of Sufentanil
Authors: Gepts Elisabeth , Shafer Steven L. , Camu Frederic , Stanski Donald R. , Woestenborghs Robert , Van Peer Achiel , Heykants Jos J.P.
Published: November 2003

Background

The pharmacokinetic profiles of sufentanil available in the literature are conflicting because of methodologic differences. Length of sampling and assay sensitivity are key factors involved in accurately estimating the volumes of distribution, clearances, and elimination phase. The unit disposition function of increasing doses of sufentanil were investigated and the influence of dose administered on the linearity of pharmacokinetics was assessed.
Inhalation Toxicity Study of a Haloalkene Degradant of Sevoflurane, Compound A (PIFE), in Sprague-Dawley Rats
Authors: Keller K. A. , Callan C. , Prokocimer P. , Delgado-Herrera L. , Friedman M. B. , Hoffman G. M. , Wooding W. L. , Cusick P. K. , Krasula R. W.
Published: November 2003

Background

Under certain circumstances in the clinical setting, contact of the anesthetic sevoflurane with a CO2absorbant (e.g., soda lime, Baralyme) leads to the formation of a degradant designated as pentafluoroisopropenyl fluoromethyl ether (PIFE; Compound A). Previous studies have shown that the kidney is the primary target organ for toxicity in the rat. This study was designed to determine the impact of PIFE on rat renal histology correlated with functional changes. The findings are discussed in terms of probable mechanism of action and relevance to humans.
Propofol Reduces Neuronal Transmission Damage and Attenuates the Changes in Calcium, Potassium, and Sodium during Hyperthermic Anoxia in the Rat Hippocampal Slice
Authors: Amorim Pedro , Chambers Geoffrey , Cottrell James , Kass Ira S.
Published: November 2003

Background

Propofol reduces cerebral blood flow, cerebral metabolic rate for oxygen, and intracranial pressure and is being increasingly used in neuroanesthesia. In vivo studies have yielded conflicting results on its ability to protect against ischemic brain damage. In the current study, an in vitro model was used to examine the mechanism of propofol's action on anoxic neuronal transmission damage.
Calcium Administration Augments Pancreatic Injury and Ectopic Trypsinogen Activation after Temporary Systemic Hypotension in Rats
Authors: Mithofer Kai , Warshaw Andrew L. , Frick Thomas W. , Lewandrowski Kent B. , Koski Greg , Rattner David W. , Fernandez-del Castillo Carlos
Published: November 2003

Background

Calcium infusion and hypotension have been described as the most important risk factors for pancreatic injury after cardiopulmonary bypass.
Inhibitory Effects of Thiopental, Ketamine, and Propofol on Voltage-dependent Calcium sup 2+ Channels in Porcine Tracheal Smooth Muscle Cells
Authors: Yamakage Michiaki , Hirshman Carol A. , Croxton Thomas L.
Published: November 2003

Background

Intravenously administered anesthetics directly inhibit airway smooth muscle contraction. Because many anesthetic agents affect membrane ion channel function and sustained contraction of airway smooth muscle requires the influx of Calcium2+ through voltage-dependent Calcium2+ channels, it was hypothesized that intravenous anesthetics inhibit airway smooth muscle voltage-dependent Calcium2+ channels.
Cerebral Vasoconstriction by Indomethacin in Intracranial Hypertension: An Experimental Investigation in Pigs
Authors: Nilsson F. , Bjorkman S. , Rosen I. , Messeter K. , Nordstrom C.-H.
Published: November 2003

Background

Uncontrolled increase in intracranial pressure is the most significant cause of mortality in patients with severe traumatic brain lesions, and the efficacy of common nonsurgical treatments has been questioned. Pharmacologically induced cerebral vasoconstriction aiming at a decrease of cerebral blood volume and brain edema has recently been suggested as an alternative. Limited clinical experience with indomethacin as a cerebral vasoconstrictor has been reported but dose- or concentration-effect relationships were not investigated. In particular, there is a lack of data showing whether a therapeutic window exists in which risk of cerebral ischemia is minimized.
Quaternary Ammonium Derivative of Lidocaine as a Long-acting Local Anesthetic
Authors: Wang G. K. , Quan C. , Vladimirov M. , Mok W. M. , Thalhammer J. G.
Published: November 2003

Background

Use of long-acting local anesthetics that elicit complete neural blockade for more than 3 h often is desirable in pain management. Unfortunately, clinically available local anesthetics are in general not suitable for prolonged analgesia. This report describes the organic synthesis and functional testing of a lidocaine derivative that appears to fulfill the criteria of long-acting local anesthetics.
Electroencephalogram Bispectral Analysis Predicts the Depth of Midazolam-induced Sedation
Authors: Liu Jin , Singh Harbhej , White Paul F.
Published: November 2003

Background

The electroencephalogram (EEG) has been used to study the effects of anesthetic and analgesic drugs on central nervous system function. A prospective study was designed to evaluate the accuracy of various EEG parameters for assessing midazolam-induced sedation during regional anesthesia.

Methods

Twenty-six consenting adult patients were administered 4.5-20 mg intravenous midazolam (in increments of 0.5-1 mg bolus doses every 6-10 min) until they became unresponsive to tactile stimulation (i.e., mild prodding or shaking). The EEG was continuously recorded from a bifrontal montage (FP1-Cz and FP2-Cz) to obtain the bispectral index (BI), 95% spectral edge frequency (SEF), median frequency (MF), and delta, theta, alpha, and beta power bands. Sedation was assessed clinically at 6-10-min intervals using the Observers' Assessment of Alertness/Sedation (OAA/S) scale, with 1 = no response (unconsciousness) to tactile stimulation to 5 = wide awake. The EEG parameters were correlated with the OAA/S scores using nonparametric Spearman's rank-correlation analysis. Kruskal-Wallis analysis of variance was used to determine significant changes in EEG parameters during the onset of and recovery from midazolam-induced sedation.

Results

Of the EEG parameters studied, the BI exhibited the best correlation with OAA/S scores during both the onset (Spearman's Rho = 0.815) and recovery (Spearman's Rho = 0.596) phases. With increasing sedation, there was a progressive decrease in the BI (OAA/S score of 5: BI = 95.4 +/- 2.3; 4: 90.3 +/- 4.5; 3:86.6 +/- 4.6; 2:75.6 +/- 9.7; 1:69.2 +/- 13.9). A similar pattern was found for the 95% SEF as the OAA/S score decreased from 4 to 1. Similarly, EEG-BI increased with recovery from the sedative effects of midazolam (OAA/S score = 2:BI = 75.2 +/- 10.2; 3:82.3 +/- 7.3; 4:90.8 +/- 6). However, no consistent changes were found with the other EEG parameters. The mean EEG values between OAA/S scores 3 and 2 and between OAA/S scores 2 and 1 during the onset and recovery phases from midazolam-induced sedation, defined as EEG50 values for response to verbal command (EEG50-VC) and to shaking of the head (EEG50-SH), were 79.3 +/- 8 and 70.8 +/- 14.3, respectively, for EEG-BI. The EEG-BI displayed the smallest coefficients of variation for the EEG50-VC and EEG50-SH values.

Conclusions

The EEG-BI appears to be a useful parameter for assessing midazolam-induced sedation and can predict the likelihood of a patient responding to verbal commands or to shaking of the head during midazolam-induced sedation.
Comparison of the Spinal Actions of the micro-Opioid Remifentanil with Alfentanil and Morphine in the Rat
Authors: Buerkle Hartmut , Yaksh Tony L.
Published: November 2003

Background

mu-Opioids administered spinally produce a potent, dose-dependent analgesic response in preclinical and clinical investigations. Side-effect profile of these compounds may be altered as a function of pharmacokinetics. The effects of intrathecal and intraperitoneal remifentanil, an esterase-metabolized mu opioid, alfentanil, and morphine were compared.

Methods

Intrathecal and intraperitoneal remifentanil, alfentanil, and morphine were examined in rats tested for hind-paw thermal withdrawal latency. The antinociceptive response was assessed and in parallel a scoring of four different parameters summarized as a supraspinal index to assess supraspinal side-effect profiles after the several drugs were delivered by the different routes.

Results

All opioids produced a dose-dependent analgesic response after intrathecal administration. The ordering of potency (intrathecal ED50 in micrograms) was remifentanil (0.7) > morphine (12.0) > alfentanil (16.3) > GR90291, principal remifentanil metabolite (> 810 micrograms). Time until onset of analgesia after intrathecal or intraperitoneal delivery was morphine > remifentanil = alfentanil. When matched for analgesic effect, the relative duration of action was morphine > alfentanil > remifentanil. The supraspinal index showed a dose-dependent increase for all agents. All intraperitoneal drugs showed dose-dependent increases in antinociception with potency (intraperitoneal ED50 in micrograms) of remifentanil (4.3) > alfentanil (24.4) > morphine (262). Calculation of intrathecal or intraperitoneal ratios for supraspinal side effects/analgesia (supraspinal index ED50/analgesia ED50) revealed remifentanil to be greatest when intrathecally administered: remifentanil (4 intrathecal: 1.4 intraperitoneal); alfentanil (0.7 intrathecal: 1.5 intraperitoneal); and morphine (1 intrathecal: 5.6 intraperitoneal).

Conclusions

These observations indicate that remifentanil has a powerful spinal opioid action. Consistent with its lipid-solubility, it has an early onset like alfentanil but displays a shorter duration of action after bolus delivery. Despite lipid solubility, remifentanil has a significant spinal therapeutic ratio. These observations likely reflect the rapid inactivation of systemically redistributed agent by plasma esterases.
Interaction of Nondepolarizing Muscle Relaxants with M2and M3Muscarinic Receptors in Guinea Pig Lung and Heart
Authors: Okanlami Olubunmi A. , Fryer Allison D. , Hirshman Carol
Published: November 2003

Background

Neuromuscular blocking agents such as gallamine and pancuronium bind to muscarinic cholinergic receptors and alter parasympathetically mediated airway caliber and heart rate. In the lungs, acetylcholine induces bronchoconstriction via M3 muscarinic receptors on airway smooth muscle, whereas in the heart M2 muscarinic receptors mediate bradycardia. Moreover, release of acetylcholine from parasympathetic nerves in the lung is decreased by inhibitory M2 receptors on the nerves, which represent a negative feedback system. Blockade of these receptors potentiates vagally induced bronchoconstriction, which may be clinically important if the M3 receptors on airway muscle are not blocked. These experiments were designed to examine the effects of the newer, nondepolarizing muscle relaxants pipecuronium, doxacurium, and mivacurium on pulmonary and cardiac muscarinic receptors.

Methods

Guinea pigs were anesthetized with urethane, paralyzed with succinylcholine, and their lungs mechanically ventilated. Pulmonary inflation pressure and heart rate were measured before and after electrical stimulation of both vagus nerves to evaluate prejunctional M2 muscarinic receptor function and after intravenous acetylcholine to evaluate postjunctional M3 and M2 receptor function in the presence of increasing concentrations of pancuronium, mivacurium, pipecuronium, and doxacurium.

Results

Pancuronium was an antagonist for M2 and M3 muscarinic receptors. Mivacurium was a more potent antagonist of M3 than M2 receptors. Pipecuronium was an antagonist of M2 but not M3 receptors. Doxacurium was not an antagonist of either M2 or M3 muscarinic receptors. Only pancuronium and pipecuronium potentiated vagally induced bronchoconstriction. With pipecuronium, the potentiation occurred at concentrations greater than those used clinically.

Conclusions

Although pipecuronium is an M2 receptor antagonist with no M3 receptor antagonist properties, potentiation of reflex-induced bronchoconstriction is unlikely, because this effect occurred only at doses greater than those used clinically.
New Ultrathin-walled Endotracheal Tube with a Novel Laryngeal Seal Design
Authors: Reali-Forster Chiara , Kolobow Theodor , Giacomini Matteo , Hayashi Tomayoshi , Horiba Koji , Ferrans Victor J.
Published: November 2003

Background

A new endotracheal tube (ETT) was fabricated and tested in sheep. It had no tracheal cuff; airway seal was achieved at the level of the glottis through a no-pressure seal made of "gills"; the laryngeal portion was oval-shaped; and the wall thickness was reduced to 0.2 mm.

Methods

Sheep were tracheally intubated either with a standard tube or with the new tube, and their lungs were mechanically ventilated for 1 or 3 days. Air leak was recorded at different peak inspiratory pressures (PIPs). Liquid seepage into the trachea was assessed using an indicator dye. Tracheolaryngeal lesions were scored grossly and histologically.

Results

There was no air leak up to 40 cmH2O of PIP, in either group, in short- and long-term studies. Methylene blue leaked across the cuff in two sheep with standard ETTs. No dye leaked across the gills with the new ETTs. In the new ETT group, the trachea appeared better preserved, grossly and histologically, than in the standard ETT group at both 1 and 3 days (P < 0.05). At day 1, the larynx and vocal cords appeared grossly less injured in the new ETT group (P < 0.05), whereas there was no difference at day 3. Histology did not show significant difference on vocal cords, epiglottis, and larynx between the two groups at any time.

Conclusions

The novel, no-pressure seal design of the new ETT is highly effective in preventing air leak and aspiration. It causes no significant tracheal injury.
Muscarinic Signaling in the Central Nervous System
Authors: Durieux Marcel E.
Published: November 2003

During the last decade, major advances have been made in our understanding of the physiology and pharmacology of CNS muscarinic signaling. It is time to emphasize that the well-known peripheral parasympathetic and cardiovascular actions represent only one component of muscarinic signaling. Interestingly, many new findings have the potential to influence the practice of anesthesiology. Inhibition of muscarinic signaling may explain some of the anesthetic state, and subtype-selective drugs may allow wider perioperative manipulation of CNS muscarinic systems. The next years will doubtlessly see progress in this area, and our specialty may well reap the benefits.
Pharmacokinetics of Cisatracurium in Patients Receiving Nitrous Oxide/Opioid/Barbiturate Anesthesia
Authors: Lien Cynthia A. , Schmith Virginia D. , Belmont Matthew R. , Abalos Amy , Kisor David F. , Savarese John J.
Published: November 2003

Background

Cisatracurium, one of the ten isomers in atracurium, is a nondepolarizing muscle relaxant with an intermediate duration of action. It is more potent and less likely to release histamine than atracurium. As one of the isomers composing atracurium, it presumably undergoes Hofmann elimination. This study was conducted to describe the pharmacokinetics of cisatracurium and its metabolites and to determine the dose proportionality of cisatracurium after administration of 2 or 4 times the ED(95).

Methods

Twenty ASA physical status 1 or 2 patients undergoing elective surgery under nitrous oxide/opioid/barbiturate anesthesia were studied. Patients received a single rapid intravenous bolus does of 0.1 or 0.2 mg x kg-1 (2 or 4 times the ED(95), respectively) cisatracurium. All patients were allowed to recover spontaneously to a train-of-four ratio > or = 0.70 after cisatracurium-induced neuromuscular block. Plasma was extracted, acidified, and stored frozen before analysis for cisatracurium, laudanosine, the monoquaternary acid, and the monoquaternary alcohol metabolite.

Results

The clearances (5.28 +/- 1.23 vs. 4.66 +/- 0.67 ml x min(-1) x kg(-1) and terminal elimination half-lives (22.4 +/- 2.7 vs. 25.5 +/- 4.1 min) were not statistically different between patients receiving 0.1 mg x kg(-1) and 0.2 mg x kg(-1), respectively. Maximum concentration values for laudanosine averaged 38 +/- 21 and 103 +/- 34 ng x ml(-1) for patients receiving the 0.1 and 0.2 mg x kg(-1) doses, respectively. Maximum concentration values for monoquaternary alcohol averaged 101 +/- 27 and 253 +/- 51 ng x ml(-1), respectively. Monoquaternary acid was not quantified in any plasma sample.

Conclusions

Cisatracurium undergoes Hofmann elimination to form laudanosine. The pharmacokinetics of cisatracurium are independent of dose after single intravenous doses of 0.1 and 0.2 mg x kg(-1).
Dose Responses for Neostigmine and Edrophonium as Antagonists of Mivacurium in Adults and Children
Authors: Bevan Joan C. , Tousignant Claude , Stephenson Catherine , Blackman Lee , Reimer Eleanor , Smith Michael F. , Bevan David R.
Published: November 2003

Background

Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children.

Methods

Fifty-four adults, aged 40.1 +/- 10.9 yr, and 54 children, aged 4.9 +/- 0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg x kg(-1) intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micrograms x kg(-1)) or edrophonium (100, 200, 400, and 1,000 micrograms x kg(-1)) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min.

Results

Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97 +/- 2% (SD) in children compared with 69 +/- 11% in adults and train-of-four to 84 +/- 5% versus 30 +/- 13% (P<0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children.

Conclusions

Spontaneous recovery from mivacurium- induced neuromuscular block is more rapid in children than in adults. Ten minutes after attempted reversal, recovery is accelerated by edrophonium and usually by neostigmine in adults but not in children. Thus, when reversal is required, edrophonium may be preferred to neostigmine.
Residual Block after Mivacurium with or without Edrophonium Reversal in Adults and Children
Authors: Bevan David R. , Kahwaji Raymond , Ansermino John M. , Reimer Eleanor , Smith Michael F. , O'Connor Gerard A. R. , Bevan Joan C.
Published: November 2003

Background

The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit.

Methods

In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode.

Results

Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P<0.01), TOF was >0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P<0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was <0.7 in four others), compared with TOF <0.7 in only one of the edrophonium group (P<0.05).

Conclusions

This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.
Propofol Alters Left Ventricular Afterload as Evaluated by Aortic Input Impedance in Dogs
Authors: Lowe Dermot , Hettrick Douglas A. , Pagel Paul S. , Warltier David C.
Published: November 2003

Background

Systemic vascular resistance incompletely describes left ventricular afterload because of the phasic nature of arterial pressure and blood flow. Aortic input impedance is an experimental description of left ventricular afterload that incorporates the frequency- dependent characteristics and viscoelastic properties of the arterial system. The effects of propofol on aortic input impedance were examined using three variables derived from the three-element Windkessel model: characteristic aortic impedance, total arterial compliance, and total arterial resistance.

Methods

Eight dogs were chronically instrumented for measurement of aortic pressure, left ventricular pressure, +dP/dt, subendocardial segment length, and aortic blood flow. Systemic hemodynamics and aortic blood pressure and flow waveforms were recorded in the conscious state and after a bolus of 5 mg x kg(-1) propofol and infusion for 15 min at 25, 50 and 100 mg x kg(-1) x h(-1). Aortic input impedance spectra were generated using power spectral analysis of aortic pressure and flow waveforms corrected for the phase responses of the pressure and flow transducers. Characteristic aortic impedance, total arterial resistance, and total arterial compliance were calculated from the aortic input impedance spectrum and the aortic pressure waveform. Parameters describing the net site and magnitude or arterial wave reflection were determined from aortic impedance.

Results

Propofol decreased total arterial resistance (3.05 +/- 0.20 during control to 2.29 +/- 0.18 dynes x s x cm(-5) x 10(3) at the high dose) and increased total arterial compliance (0.53 +/- 0.04 during control to 1.15 +/- 0.17 ml x mmHg(-1) at the high dose) in a dose- related manner. Propofol increased characteristic aortic impedance (1.49 +/- 0.15 during control to 2.20 +/- 0.20 dynes x s x cm(-5) x 10(2) at the high dose). The net site and the magnitude of arterial wave reflection were unchanged by the propofol.

Conclusions

In chronically instrumented dogs, propofol decreased total arterial resistance, a property of arteriolar resistance vessels, consistent with the known actions of this drug on systemic vascular resistance. Propofol also increased total arterial compliance and characteristic aortic impedance, indicating that this anesthetic affects the mechanical properties of the aorta. Propofol had no effect on arterial wave reflection patterns. The results indicate that propofol reduces left ventricular afterload via decreases in peripheral resistance and increases in arterial compliance.