bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
Reduction of Postburn Hyperalgesia after Local Injection of Ketorolac in Healthy Volunteers
Authors: Lundell John C. , Silverman David G. , Brull Sorin J. , O'Connor Theresa Z. , Kitahata Luke M. , Collins J. G. , LaMotte Robert 
Published: November 2003

Background
Nonsteroidal antiinflammatory drugs may be particularly effective against prostaglandin-mediated, post-injury hyperalgesia and related inflammatory pain. However, their usefulness may be limited by their systemic side effects. The current study determined if local effectiveness can be achieved by low-dose intradermal nonsteroidal antiinflamatory drug administration.

Methods
Ten healthy volunteers were asked to make magnitude estimations of the pain induced by a contact thermal stimulator at 1 degree C increments between 43 and 51 degrees C at three 1 x 1 cm study sites on each forearm during three study phases:(1) baseline; (2) after pretreatment with 10 microl 0.9% saline (n=1 site on each forearm), 0.3 mg ketorolac (n=1 on each forearm), or nothing (n=1 on each forearm); and (3) after "injury" by a mild burn at the ketorolac- and saline-treated sites on one arm or by injection of 10 nmol bradykinin at all three sites on the other arm. The effects of pretreatment on the pain induced by thermal testing were assessed using repeated-measures analysis of variance.

Results
Pretreatment with ketorolac had a selective effect on the postburn injury hyperalgesia, reducing the increase in pain intensity (P<0.05) but not the decline in pain threshold. It had no effect on the responses to thermal stimuli before injury or on the pain of burning, which were similar at ketorolac- and saline-treated sites. The effect of pretreatment with ketorolac on bradykinin-induced hyperalgesia was not achieved after bradykinin injection at sites pretreated with saline as well as ketorolac.
Intravenous Lidocaine and Bupivacaine Dose-dependently Attenuate Bronchial Hyperreactivity in Awake Volunteers
Authors: Groeben Harald , Schwalen Andreas , Irsfeld Stefan , Stieglitz Sven , Lipfert Peter , Hopf Hans-Bernd 
Published: November 2003

Background
In standard textbooks, intravenous lidocaine is recommended for intubation of patients with bronchial hyperreactivity. However, whether and to what extent intravenous local anesthetics attenuate bronchial hyperreactivity in humans is unknown. Accordingly, nine awake volunteers with known bronchial hyperreactivity were subjected to an inhalational challenge with acetylcholine before and during intravenous infusion of lidocaine, bupivacaine, or placebo in a randomized, double-blinded fashion.

Methods
Baseline acetylcholine threshold concentrations were determined 3-5 days before initiation of the investigation. The response to the acetylcholine challenge was defined as hyperreactive, if forced expiratory volume in 1 s decreased by at least 20%. In addition, the acetylcholine threshold for a 100% increase in airway resistance was obtained by body plethysmography. On seven different days, the acetylcholine challenge was repeated at the end of a 30-min intravenous infusion period of three doses of lidocaine (1, 3, and 6 mg.min(-1)) or bupivacaine (0.25, 0.75, and 1.5 mg.min(-1)), during saline placebo infusion, respectively. Acetylcholine-threshold concentrations were presented with the respective plasma concentrations of the local anesthetic.

Results
The infusion of lidocaine and bupivacaine resulted in plasma concentrations (means +/- SD) of 0.29 +/- 0.11, 1.14 +/- 0.39, and 2.02 +/- 0.5 microg.ml(-1) for lidocaine and 0.11 +/- 0.04, 0.31 +/- 0.09, and 0.80 +/- 0.18 microg.ml(-1) for bupivacaine, respectively. Compared to baseline, the acetylcholine threshold for a 20% decrease of forced expiratory volume in 1 s as well as the threshold for a 100% increase in total airway resistance increased significantly with increasing plasma concentrations of both local anesthetics. Compared to placebo, acetylcholine threshold was almost quadrupled for lidocaine and tripled for bupivacaine with the highest plasma concentration of each local anesthetic.

Conclusions
In awake humans, intravenous lidocaine and bupivacaine both dose-dependently attenuated the hyperreactive response to a nonspecific inhalational challenge with acetylcholine.