bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Halothane and Sevoflurane on Inhibitory Neurotransmission to Medullary Expiratory Neurons in a Decerebrate Dog Model
Authors: Stucke Astrid G. , Stuth Eckehard A. E. , Tonkovic-Capin Viseslav , Tonkovic-Capin Mislav , Hopp Francis A. , Kampine John P. , Zuperku Edward J. 
Published: August 2004

Background
In canine expiratory bulbospinal neurons, 1 minimum alveolar concentration (MAC) halothane and sevoflurane reduced the glutamatergic excitatory drive at a presynaptic site and enhanced the overall gamma-aminobutyric acid (GABA)-mediated inhibitory input. The authors investigated if this inhibitory enhancement was mainly caused by postsynaptic effects.

Methods
Two separate anesthetic studies were performed in two sets of decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 MAC halothane or sevoflurane on extracellularly recorded neuronal activity was measured during localized picoejection of the GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline. Complete blockade of GABAA-mediated inhibition with bicuculline was used to assess the prevailing overall inhibitory input to the neuron. The neuronal response to muscimol was used to estimate the anesthetic effect on postsynaptic GABAA receptor function.

Results
Halothane at 1 MAC depressed the spontaneous activity of 12 expiratory neurons 22.2 +/- 14.8% (mean +/- SD) and overall glutamatergic excitation 14.5 +/- 17.9%. Overall GABA-mediated inhibition was enhanced 14.1 +/- 17.9% and postsynaptic GABAA receptor function 74.2 +/- 69.2%. Sevoflurane at 1 MAC depressed the spontaneous activity of 23 neurons 20.6 +/- 19.3% and overall excitation 10.6 +/- 21.7%. Overall inhibition was enhanced 15.4 +/- 34.0% and postsynaptic GABAA receptor function 65.0 +/- 70.9%. The effects of halothane and sevoflurane were not statistically different.

Conclusion
Halothane and sevoflurane at 1 MAC produced a small increase in overall inhibition of expiratory premotor neuronal activity. The increase in inhibition results from a marked enhancement of postsynaptic GABAA receptor function that is partially offset by a reduction in presynaptic inhibitory input by the anesthetics.
An Isolated, Antegrade, Perfused, Peroneal Nerve Anterior Tibialis Muscle Model in the Rat
Authors: De Haes Ann , Houwertjes Martin C. , Proost Johannes H. , Wierda J. Mark K. H. 
Published: August 2004

Background
A model of an antegrade, perfused, isolated rat peroneal nerve anterior tibial muscle was developed to study potentially important factors governing the time course of action of (nondepolarizing) neuromuscular blocking agents such as concentration, blood flow, and temperature. The model allows observation of the effects of selective changes in these factors.

Methods
The authors isolated the anterior tibial muscle and cannulated the anterior tibial artery and vein, providing a way for single-pass perfusion with blood from a donor rat. A force transducer was connected to the tibialis anterior muscle and a stimulator was connected to the tibial nerve. The influence of intrinsic potency (EC90) and muscle blood flow rate on the time course of pancuronium and rocuronium was investigated.

Results
The model remained stable for at least 4 h with respect to twitch height, muscle structure and function, and blood chemistry. Doubling the muscle-blood flow resulted in a significantly faster onset and offset for both pancuronium and rocuronium. Trebling the intrinsic potency (EC90) was not associated with significant changes in the time course of action of the relaxants.

Conclusion
The authors developed and validated a model that allows us to study biophase kinetics of neuromuscular blocking agents in the anterior tibial muscle of the rat. In this model, muscle-blood flow rather than EC90 appears to predominantly determine the onset and offset time of nondepolarizing muscle relaxants.
Does the Immobilizing Effect of Thiopental in Brain Exceed That of Halothane?
Authors: Antognini Joseph F. , Carstens Earl , Atherley Richard 
Published: August 2004

Background
Recent studies suggest that anesthetics such as isoflurane act in the spinal cord to suppress movement that occurs during noxious stimulation. The authors examined the effect of halothane and thiopental on suppression of noxious-evoked movement using a model of differential anesthetic delivery. They hypothesized that halothane and thiopental, similar to isoflurane, would suppress movement primarily via an action in spinal cord.

Methods
Goats were anesthetized and prepared for differential anesthetic delivery. Anesthesia was maintained with halothane (n = 5) or thiopental (n = 5). Anesthetic requirements were determined (noxious clamp on a dewclaw for 1 min) during halothane or thiopental (via infusion) delivery to the whole body and delivery only to the head.

Results
Control (whole body) halothane requirement was 0.9 +/- 0.2%; halothane requirement in the head during differential delivery was 3.4 +/- 1% (P < 0.01). During selective halothane delivery, the electroencephalogram was greatly depressed or was isoelectric even though the animals moved during noxious stimulation. Control (whole body) plasma thiopental requirement was 20 +/- 10 microg/ml. When thiopental was selectively delivered to the head, the electroencephalogram was active in all five animals, and cranial thiopental requirement was 42 +/- 6 microg/ml (P < 0.01).

Conclusion
These data suggest that halothane and thiopental, like isoflurane, act in spinal cord to suppress movement occurring with noxious stimulation. However, halothane appears to be less potent in the brain as evidenced by the electroencephalogram data, suggesting that action in spinal cord plays a more significant role for halothane than for thiopental.
Droperidol Inhibits GABAAand Neuronal Nicotinic Receptor Activation
Authors: Flood Pamela , Coates Kristen M. 
Published: August 2004

Background
Droperidol is used in neuroleptanesthesia and as an antiemetic. Although its antiemetic effect is thought to be caused by dopaminergic inhibition, the mechanism of droperidol's anesthetic action is unknown. Because gamma-aminobutyric acid type A (GABAA) and neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated as putative targets of other general anesthetic drugs, the authors tested the ability of droperidol to modulate these receptors.

Methods
gamma-Aminobutyric acid type A alpha1beta1gamma2 receptor, alpha7 and alpha4beta2 nAChRs were expressed in Xenopus oocytes and studied with two-electrode voltage clamp recording. The authors tested the ability of droperidol at concentrations from 1 nm to 100 microm to modulate activation of these receptors by their native agonists.

Results
Droperidol inhibited the GABA response by a maximum of 24.7 +/- 3.0%. The IC50 for inhibition was 12.6 +/- 0.47 nm droperidol. At high concentrations, droperidol (100 microm) activates the GABAA receptor in the absence of GABA. Inhibition of the GABA response is significantly greater at hyperpolarized membrane potentials. The activation of the alpha7 nAChR is also inhibited by droperidol, with an IC50 of 5.8 +/- 0.53 microm. The Hill coefficient is 0.95 +/- 0.1. Inhibition is noncompetitive, and membrane voltage dependence is insignificant.

Conclusions
Droperidol inhibits activation of both the GABAA alpha1beta1gamma2 and alpha7 nAChR. The submaximal GABA inhibition occurs within a concentration range such that it might be responsible for the anxiety, dysphoria, and restlessness that limit the clinical utility of high-dose droperidol anesthesia. Inhibition of the alpha7 nAChR might be responsible for the anesthetic action of droperidol.
Non–steady State Analysis of the Pharmacokinetic Interaction between Propofol and Remifentanil
Authors: Bouillon Thomas , Bruhn Joergen , Radu-Radulescu Lucian , Bertaccini Edward , Park Sang , Shafer Steven 
Published: August 2004

Background
The pharmacokinetics of both propofol and remifentanil have been described extensively. Although they are commonly administered together for clinical anesthesia, their pharmacokinetic interaction has not been investigated so far. The purpose of the current investigation was to elucidate the nature and extent of pharmacokinetic interactions between propofol and remifentanil.

Methods
Twenty healthy volunteers aged 20-43 yr initially received either propofol or remifentanil alone in a stepwise incremental and decremental fashion a target controlled infusion. Thereafter, the respective second drug was infused to a fixed target concentration in the clinical range (0-4 microg/ml and 0-4 ng/ml for propofol and remifentanil, respectively) and the stepwise incremental pattern repeated. Frequent blood samples were drawn for up to 6 h for propofol and 40 min for remifentanil after the end of administration and assayed for the respective drug concentrations with gas chromatography-mass spectrometry. The time courses of the measured concentrations were fitted to standard compartmental models. Calculations were performed with NONMEM. After having established the individual population models for both drugs and an exploratory analysis for hypothesis generation, pharmacokinetic interaction was identified by including an interaction term into the population model and comparing the value of the objective function in the presence and absence of the respective term.

Results
The concentration-time courses of propofol and remifentanil were described best by a three- and two-compartment model, respectively. In the concentration range examined, remifentanil does not alter propofol pharmacokinetics. Coadministration of propofol decreases the central volume of distribution and distributional clearance of remifentanil by 41% and elimination clearance by 15%. This effect was not concentration-dependent in the examined concentration range of propofol.

Conclusions
Coadministration of propofol decreases the bolus dose of remifentanil needed to achieve a certain plasma-effect compartment concentration but does not alter the respective maintenance infusion rates and recovery times to a clinically significant degree.
Propofol
Authors: Ludbrook Guy L. , Visco Elizabeth , Lam Arthur M. 
Published: August 2004

Background
The potential benefit of propofol dose regimens that use physiologic pharmacokinetic modeling to target the brain has been demonstrated in animals, but no data are available on the rate of propofol distribution to the brain in humans. This study measured the brain uptake of propofol in humans and the simultaneous effects on electroencephalography, cerebral blood flow velocity (V(mca)), and cerebral oxygen extraction.

Methods
Seven subjects had arterial and jugular bulb catheters placed before induction. Electroencephalography and V(mca) were recorded during induction with propofol while blood samples were taken from both catheters for later propofol analysis. Brain uptake of propofol was calculated using mass balance principles, with effect compartment modeling used to quantitate the rate of uptake.

Results
Bispectral index (electroencephalogram) values decreased to a minimum value of approximately 4 at around 7 min from the onset of propofol administration and then slowly recovered. This was accompanied by decreases in V(mca), reaching a minimum value of approximately 40% of baseline. Cerebral oxygen extraction did not change, suggesting parallel changes in cerebral metabolism. There was slow equilibrium of propofol between the blood and the brain (t(1/2keo) of 6.5 min), with a close relation between brain concentrations and bispectral index, although with considerable interpatient variability. The majority of the decreases in V(mca), and presumably cerebral metabolism, corresponded with bispectral index values reaching 40-50 and the onset of burst suppression.

Conclusion
Description of brain distribution of propofol will allow development of physiologic pharmacokinetic models for propofol and evaluation of dose regimens that target the brain.
Validation Study of Two-microphone Acoustic Reflectometry for Determination of Breathing Tube Placement in 200 Adult Patients
Authors: Raphael David T. , Benbassat Maxim , Arnaudov Dimiter , Bohorquez Alex , Nasseri Bita 
Published: August 2004

Background
Acoustic reflectometry allows the construction of a one-dimensional image of a cavity, such as the airway or the esophagus. The reflectometric area-distance profile consists of a constant cross-sectional area segment (length of endotracheal tube), followed either by a rapid increase in the area beyond the carina (tracheal intubation) or by an immediate decrease in the area (esophageal intubation).

Methods
Two hundred adult patients were induced and intubated, without restrictions on anesthetic agents or airway adjunct devices. A two-microphone acoustic reflectometer was used to determine whether the breathing tube was placed in the trachea or esophagus. A blinded reflectometer operator, seated a distance away from the patient, interpreted the acoustic area-distance profile alone to decide where the tube was placed. Capnography was used as the gold standard.

Results
Of 200 tracheal intubations confirmed by capnography, the reflectometer operator correctly identified 198 (99% correct tracheal intubation identification rate). In two patients there were false-negative results, patients with a tracheal intubation were interpreted as having an esophageal intubation. A total of 14 esophageal intubations resulted, all correctly identified by reflectometry, for a 100% esophageal intubation identification rate.

Conclusions
Acoustic reflectometry is a rapid, noninvasive method by which to determine whether breathing tube placement is correct (tracheal) or incorrect (esophageal). Reflectometry determination of tube placement may be useful in airway emergencies, particularly in cases where visualization of the glottic area is not possible and capnography may fail, as in patients with cardiac arrest.
Pharmacodynamics and Pharmacokinetics of Propofol in a Medium-Chain Triglyceride Emulsion
Authors: Ward Denham S. , Russell Norton J. , Guivarc'h Pol-Henri , Litman Ronald S. , Bailey Peter L. 
Published: August 2004

Background
Because propofol is water insoluble, current formulations of propofol use a soybean oil emulsion. These soybean emulsions cause elevated plasma triglycerides and support bacterial growth. This study compares an alternative formulation of propofol as a 2% emulsion in a medium-chain triglyceride solution (IDD-D Propofol) with Diprivan.

Methods
This double-blind, crossover, phase 1 study compared IDD-D Propofol with Diprivan using two consecutive protocols of 12 subjects each. Subjects in protocol 1 received a single bolus of 2.5 mg/kg, and those in protocol 2 received the same induction dose followed by a 30-min infusion at 0.2 mg. kg(-1).min(-1). Venous samples were taken for propofol concentration and biochemical measurements. Induction and emergence times were measured by termination of voluntary counting and responding to command, respectively.

Results
Plasma concentrations were not different between the two formulations. Induction time was 14% longer with IDD-D Propofol than with Diprivan (N = 24, protocols 1 and 2 combined, 53.3 +/- 12.1 s and 46.9 +/- 7.8 s, respectively; P = 0.002). Emergence time was not significantly different for protocol 1 but was marginally longer (P = 0.04) for IDD-D Propofol in protocol 2 (1,197 +/- 445 s [n = 11] and 1,254 +/- 468 s [n = 12], respectively). As expected because of the inherent characteristics of the formulations, plasma triglycerides were elevated for Diprivan but not for IDD-D Propofol; octanoate, a metabolite of medium-chain triglycerides, was elevated only with IDD-D Propofol. Octanoate was elevated to concentrations below those considered toxic. Plasma concentrations of other biochemical markers of medium-chain triglyceride metabolism, ketones, showed no significant changes. Interestingly, there were significant differences between male and female subjects in the propofol plasma concentrations and time to awakening with both drugs.

Conclusions
Differences between the two propofol formulations were slight and not clinically significant. Similar gender differences in plasma concentrations and awaking times were found for both formulations.
Changes of Electroencephalographic Bicoherence during Isoflurane Anesthesia Combined with Epidural Anesthesia
Authors: Hagihira Satoshi , Takashina Masaki , Mori Takahiko , Mashimo Takashi , Yoshiya Ikuto 
Published: August 2004

Background
The authors previously reported that, during isoflurane anesthesia, electroencephalographic bicoherence values changed in a fairly restricted region of frequency versus frequency space. The aim of the current study was to clarify the relation between electroencephalographic bicoherence and the isoflurane concentration.

Methods
Thirty elective abdominal surgery patients (male and female, aged 34-77 yr, American Society of Anesthesiologists physical status I-II) were enrolled. After electroencephalogram recording with patients in an awake state, anesthesia was induced with 3 mg/kg thiopental and maintained with oxygen and isoflurane. Continuous epidural anesthesia with 80-100 mg/kg 1% lidocaine was also administered. Using software they developed, the authors continuously recorded the FP1-A1 lead of the electroencephalographic signal and expired isoflurane concentration to an IBM-PC compatible computer. After confirming the steady state of each isoflurane (end-tidal concentration at 0.3, 0.5, 0.7, 0.9, 1.1, 1.3, and 1.5%), electroencephalographic bicoherence values were calculated.

Results
In a light anesthetic state, electroencephalographic bicoherence values were low (generally < or = 15.0%). At increased concentrations of isoflurane, two peaks of electroencephalographic bicoherence emerged along the diagonal line (f1=f2). The peak emerged at around 4.0 Hz and grew higher as isoflurane concentration increased until it reached a plateau (43.8 +/- 3.5%, mean +/- SD) at isoflurane 0.9%. The other peak, at about 10.0 Hz, also became significantly higher and reached a plateau (32.6 +/- 9.2%) at isoflurane 0.9%; at isoflurane 1.3%, however, this peak slightly decreased.

Conclusion
Changes in the height of two electroencephalographic bicoherence peaks correlated well with isoflurane concentration.
Propofol and Sevoflurane in Subanesthetic Concentrations Act Preferentially on the Spinal Cord
Authors: Kammer Thomas , Rehberg Benno , Menne Dieter , Wartenberg Hans-Christian , Wenningmann Ingobert , Urban Bernd W. 
Published: August 2004

Background
Animal experiments in recent years have shown that attenuation of motor responses by general anesthetics is mediated at least partly by spinal mechanisms. Less is known about the relative potency of anesthetic drugs in suppressing cortical and spinal electrophysiological responses in vivo in humans, particularly those, but not only those, connected with motor responses. Therefore, we studied the effects of sevoflurane and propofol in humans using multimodal electrophysiological assessment.

Methods
We studied nine healthy volunteers in two sessions during steady state sedation with 0.5, 1.0, and 1.5 microg/l (targeted plasma concentration) propofol or 0.2 and 0.4 vol% (end-tidal) sevoflurane. Following a 15-min equilibration period, motor responses to transcranial magnetic stimulation and peripheral (H-reflex, F-wave) stimulation were recorded, while electroencephalography and auditory evoked responses were recorded in parallel.

Results
At concentrations corresponding to two thirds of C(50 awake), motor responses to transcranial magnetic stimulation were reduced by approximately 50%, H-reflex amplitude was reduced by 22%, F-wave amplitude was reduced by 40%, and F-wave persistence was reduced by 25%. No significant differences between sevoflurane and propofol were found. At this concentration, the Bispectral Index was reduced by 7%, and the middle-latency auditory evoked responses were attenuated only mildly (N(b) latency increased by 11%, amplitude P(a)N(b) did not change). In contrast, the postauricular reflex was suppressed by 77%.

Conclusions
The large effect of both anesthetics on all spinal motor responses, compared with the small effect on electroencephalography and middle-latency auditory evoked responses, assuming that they represent cortical modulation, may suggest that the suppression of motor responses to transcranial magnetic stimulation is largely due to submesencephalic effects.
Conventional Mechanical Ventilation Is Associated with Bronchoalveolar Lavage-induced Activation of Polymorphonuclear Leukocytes
Authors: Zhang Haibo , Downey Gregory P. , Suter Peter M. , Slutsky Arthur S. , Ranieri V. Marco 
Published: August 2004

Background
Protective ventilatory strategies have resulted in a decreased mortality rate in acute respiratory distress syndrome, but the underlying mechanisms remain unclear. The authors hypothesized that (1) mechanical ventilation modulates activation of polymorphonuclear leukocytes (PMNs), (2) the consequent release of proteinases is correlated with a systemic inflammatory response and with multiple organ dysfunction, and (3) these deleterious effects can be minimized by a protective ventilatory strategy.

Methods
Human PMNs were incubated with bronchoalveolar lavage fluid obtained from patients at entry or 36 h after randomization to ventilation with either a conventional (control) or a lung-protective strategy. PMN oxidant production and surface expression of adhesion molecules and granule markers, including CD18, CD63, and L-selectin, were measured by flow cytometry. Extracellular elastase activity was quantified using a fluorescent substrate.

Results
Bronchoalveolar lavage obtained from both groups of patients at entry showed similar effects on PMN oxidant production and expression of surface markers. At 36 h, exposure of PMNs to bronchoalveolar lavage fluid from the control group resulted in increased PMN activation as manifested by a significant increase in oxidant production, CD18, and CD63 surface expression, and shedding of L-selectin. By contrast, these variables were unchanged at 36 h in the lung-protective group. There was a significant correlation between the changes of the variables and changes in interleukin-6 level and the number of failing organs.

Conclusions
Polymorphonuclear leukocytes can be activated by mechanical ventilation, and the consequent release of elastase was correlated with the degree of systemic inflammatory response and multiple organ failure. This result may possibly explain the decreased mortality in acute respiratory distress syndrome patients treated with a lung-protective strategy.