bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compound A Concentrations during Sevoflurane Anesthesia in Children
Authors: Frink Edward J. , Green William B. , Brown Elizabeth A. , Malcomson Mark , Hammond Leslie C. , Valencia Francisco G. , Brown Burnell R. 
Published: November 2003

Background
Sevoflurane is a new inhalation agent that should be useful for pediatric anesthesia. Sevoflurane undergoes degradation in the presence of carbon dioxide absorbents; however, quantification of the major degradation product (compound A) has not been evaluated during pediatric anesthesia. This study evaluates sevoflurane degradation compound concentrations during sevoflurane anesthesia using a 2-1 fresh gas flow and a circle system with carbon dioxide absorber in children with normal renal and hepatic function.

Methods
The concentrations of compound A were evaluated during sevoflurane anesthesia in children using fresh soda lime as the carbon dioxide absorbent. Nineteen patients aged 3 months-7 yr were anesthetized with sevoflurane (2.8% mean end-tidal concentration) using a total fresh gas flow of 21 in a circle absorption system. Inspiratory and expiratory limb circuit gas samples were obtained at hourly intervals, and the samples were analyzed using a gas chromatography-flame ionization detection technique. Carbon dioxide absorbent temperatures were measured in the soda lime during anesthesia for hepatic and renal function studies. Venous blood samples were obtained before anesthesia, at the end of anesthesia, and 2h after anesthesia for plasma inorganic fluoride ion concentration.

Results
The maximum inspiratory concentration of compound A was 5.4 +/- 4.4 ppm (mean +/- SD), and the corresponding expiratory concentration was 3.7 +/- 2.7 ppm (mean +/- SD). The maximum inspiratory compound A concentration in any patient was 15 ppm. Mean concentrations of compound A peaked at intubation and remained stable, declining slightly after 120 min of anesthesia. The duration of anesthesia was 240 +/- 139 min (mean +/-SD). Maximum soda lime temperature ranged between 23.1 degrees C and 40.9 degrees C. There was a positive correlation between maximum absorbent temperature and maximum compound A concentration (r2 = 0.58), as well as between the child's body surface area and maximum compound A concentration (r2 = 0.59). Peak plasma inorganic fluoride ion concentration was 21.5 +/- 6.1 microgmol/1. There were no clinically significant changes in hepatic or renal function studies performed 24 h postanesthesia.

Conclusions
Sevoflurane anesthesia of 4 h in normal children using a 2-1 flow circle system produced concentrations of compound A of 15 ppm or less. There was no evidence of abnormality of renal or hepatic function up to 24 h after anesthesia; however, larger studies will be required to confirm the absence of organ toxicity.
Dual Actions of Halothane on Intracellular Calcium Stores of Vascular Smooth Muscle
Authors: Akata Takashi , Boyle Walter A. 
Published: November 2003

Background
Halothane has been reported to affect the integrity of intracellular Ca2+ stores in a number of tissues including vascular smooth muscle. However, the actions of halothane on intracellular Ca2+ stores are not yet fully understood.

Methods
Employing the isometric tension recording method, the action of halothane in isolated endothelium-denuded rat mesenteric arteries under either intact or beta-escinmembrane-permeabilized conditions was investigated.

Results
Halothane (0.125-5%) produced concentration-dependent contractions in Ca2+ free solution in both intact and membrane-permeabilized muscle strips. Ryanodine treatment or repetitive application of phenylephrine eliminated both caffeine-and halothane-induced contractions in the Ca2+ free solution. When either halothane and caffeine, caffeine and halothane, phenylephrine and halothane, or inositol 1,4,5-triphosphate and halothane were applied consecutively in the Ca2+ free solution in either intact or membrane-permeabilized muscle strips, the contraction induced by application of the second agent of the pair was inhibited compared to application of that agent alone. However, when procaine was applied before and during application of the first agent, the contraction induced by the first agent was inhibited and the contraction induced by the second agent was restored. Heparin inhibited the inositol 1,4,5-triphosphate-mediated contraction, but not contractions induced by halothane or caffeine. Halothane (0.125-5%), applied during Ca2+ loading, produced concentration-dependent inhibition of the caffeine contraction (used to estimate the amount of Ca2+ in the store) in both intact and membrane-permeabilized muscle strips. In contrast, halothane applied with procaine during Ca2+ loading produced concentration-dependent enhancement of the caffeine contraction. This enhancement was observed only in the intact but not in the membrane-permeabilized condition.

Conclusions
Halothane has two distinct actions on the intracellular Ca2+ stores of vascular smooth muscle, a Ca2+ releasing action and a stimulating action on Ca2+ uptake. Halothane releases Ca2+ from the stores that are sensitive to both caffeine/ryanodine and phenylephrine/inositol 1,4,5-triphosphate through a procaine-sensitive mechanism. The observed inhibitory effect on Ca2+ uptake is probably caused by the Ca2+ uptake after blockade of Ca2+ release may be membrane-mediated.
Divergence of Intracranial and Central Venous Pressures in Lightly Anesthetized, Tracheally Intubated Dogs That Move in Response to a Noxious Stimulus
Authors: Lanier William L. , Albrecht Ronald F. , Iaizzo Paul A. 
Published: November 2003

Background
Intracranial pressure (ICP) may increase in tracheally intubated subjects during periods of movement (e.g, "bucking" and coughing). Recent research has suggested that factors other than passive congestion of the cerebral vessels, resulting from increases in central venous pressure, may contribute to the ICP response. The current study evaluated this issue in a canine model of intracranial hypertension and additionally evaluated the relationship between ICP and static increases in superior vena caval pressure.

Methods
Six dogs were lightly anesthetized with 0.65% end-expired halothane in oxygen and nitrogen, and ventilation was mechanically controlled. Intracranial pressure was increased to a stable baseline of 15-20 mmHg using a subarachnoid infusion of warm 0.9% saline solution. The following variables were quantified before, and for 6 min after, initiating a 1-min noxious stimulus to the trachea and skin: ICP, central venous pressure, electromyograms (masseter, deltoid, and intercostal muscles), intrathoracic pressure, and cerebral perfusion pressure (defined as mean arterial pressure -- ICP). Later, the protocol was repeated in the presence of neuromuscular block with pancuronium. Finally, in the same dogs, occlusion of the superior vena cava at its junction with the right atrium was used to increase superior vena caval pressure in 5-mmHg increments, from 5 to 30 mmHG, so that the resulting increases in ICP could be quantified.

Results
In unparalyzed dogs whose heads were maintained at the level of the right atrium, there was a 22-mmHg increase in ICP at 1 min after initiating the noxious stimulus (P<0.05). The ICP increase was related to electromyogram activation and a 6-mmHg increase in central venous pressure; however, it was not associated with significant increases in intrathoracic pressure or cerebral perfusion pressure. Treatment with pancuronium abolished the electromyographic, ICP, and central venous pressure responses to noxious stimulus. When superior vena caval pressure was statically manipulated, the resulting ICP increase was only one half the magnitude of the superior vena caval pressure increase. After elevating the head 14 cm, the ratio of ICP to superior vena pressure increases was reduced to one third.

Conclusions
If these results apply to humans, it was concluded that increases in ICP that accompany movement in tracheally intubated patients may arise from two complementary factors: (1) cerebrovascular dilation that correlates with electromyographic activity and is mediated by ascending neural pathways that transmit proprioreceptive information, and (2) passive venous congestion that results from any increase in central venous pressure. The influence of the latter factor can be reduced by elevating the head. (Key words: Blood pressure, venous pressure; mean arterial pressure. Muscle: afferent activity; electromyograms, skeletal. Neuromuscular relaxants: pancuronium.)
Insulin Treatment of Corticosteroid-associated Hyperglycemia and Its Effect on Outcome after Forebrain Ischemia in Rats
Authors: Wass Thomas C. , Scheithauer Bernd W. , Bronk James T. , Wilson Rebecca M. , Lanier William L. 
Published: November 2003

Background
Recent studies have reported that dexamethasone worsens neuronal injury after brain ischemia. This effect is assumed to be secondary to drug-induced hyperglycemia. The current study used a rat model to test the hypotheses that insulin treatment of dexamethasone-induced hyperglycemia would result in a postischemic neurologic outcome that is: (1) better than that of hyperglycemic, dexamethasone-treated subjects; and (2) better than, or equal to, that of saline-treated control subjects.

Methods
Twenty-four halothane-anesthetized (1.0% inspired) rats were randomly assigned to one of three treatment groups (N = 8 in each group): (1) normoglycemic, placebo-treated rats (group P) received an intravenous saline infusion; (2) hyperglycemic, dexamethasone-treated rats (group D) received 2 mg/kg intraperitoneal dexamethasone at days, 1 day, and h before ischemia plus an intravenous saline infusion; and (3) normoglycemic, dexamethasone- and insulin-treated rats (group DI) received the same treatment as group D, plus an intravenous insulin infusion shortly before ischemia. Blood gases and acid-base status were maintained within normal physiologic ranges. Pericranial and rectal temperatures were maintained at normothermia. Forebrain ischemia of 10 min duration was produced using an established model. Neurologic function was assessed by a blinded observer at 24 and 48 h postischemia. Brain histopathology was assessed at the time of ischemia-related death or after the examination at 48 h. All 24 rats were included in the analysis of neurologic function; however, only 21 rats that survived for > or = 24h post-ischemia were included in the histologic analysis.

Results
Rats were well matched for systemic physiologic variables, with the exception of glucose concentrations. Plasma glucose concentration immediately before ischemia was as follows: group P = 129 +/- 8 mg/dl (mean +/- SD), group D= 344 +/- 29 mg/dl, and group DI = 123 +/- 17 mg/dl. At 48h postischemia, groups P and DI were minimally injured and had similar functional scores. In contrast, all group D rats died of cerebral ischemia. Histologic injury was significantly worse in group D than in either group P or DI, but did not differ significantly between groups P and DI. When all groups were combined, there was a significant correlation between neurologic function and total histopathology score ranks.

Conclusions
In the current study, dexamethasone administration before brain ischemia resulted in a worsening of postischemic outcome that was relate to drug-induced hyperglycemia. Restoration of normoglycemia, using insulin, resulted in a functional outcome similar to that in group P, and an attenuation of dexamethasone-associated histologic injury.
Temperature Dependence of the Potency of Volatile General Anesthetics
Authors: Franks N. P. , Lieb W. R. 
Published: November 2003

Background
When performing experiments at room temperature with volatile general anesthetics and in vitro mammalian preparations (such as isolated neurons), the question arises as to which concentrations of anesthetics are "clinically relevant." Different choices can lead to different interpretations of the anesthetic sensitivities of putative target sites.

Methods
Published data on the temperature dependence of minimum alveolar concentration were analyzed.

Results
Although gas-phase potencies of volatile anesthetics increase markedly with decreasing temperature, the corresponding aqueous-phase potencies are relatively constant. Changes in minimum alveolar concentration with temperature can be accounted for, on physical grounds, in terms of the temperature dependencies of anesthetics binding to their central nervous system target sites.

Conclusion
When performing room-temperature in vitro experiments on simple mammalian preparations with a volatile anesthetic, the aqueous-phase (but not the gas- phase) minimum alveolar concentration calculated at normal body temperature is, to a first approximation, the appropriate choice for a clinically relevant anesthetic concentration. Recommended aqueous-phase minimum alveolar concentration values (in MM) for desflurane, enflurane, halothane, isoflurane, and sevoflurane have have been calculated.
Interaction of Isoflurane and Nitrous Oxide Combinations Similar for Median Electroencephalographic Frequency and Clinical Anesthesia
Authors: Ropcke Heiko , Schwilden Helmut 
Published: November 2003

Background
The volatile anesthetic sparing effect of nitrous oxide in clinical studies is less than might be expected from the additivity of minimum alveolar concentration values. Other studies identify nonadditive interactions between isoflurane and nitrous oxide. The aim of this study was to quantify the interaction of isoflurane and nitrous oxide at a constant median electroencephalographic frequency.

Methods
Twenty-five patients were studied during laparotomies. Nitrous oxide was randomly administered in concentrations of 0, 20, 40, 60, and 75 vol%, to ten patients for each nitrous oxide concentration. Isoflurane vaporizer settings were chosen so that the median electroencephalographic frequency was held between 2 and 3 Hz. The relationship between nitrous oxide concentrations and required isoflurane concentrations was examined with the method of isoboles.

Results
Nitrous oxide linearly decreased the isoflurane requirement. Addition of every 10 vol% of nitrous oxide decreases the isoflurane requirement by approximately 0.04 vol%. The total anesthetic requirement of isoflurane and nitrous oxide, expressed in terms of previously reported minimum alveolar concentration values, increased significantly with increasing nitrous oxide concentrations.

Conclusions
The interaction of isoflurane and nitrous oxide in the dose range 0-75 vol% on median electroencephalographic frequency is compatible with additivity. The potency of nitrous oxide as a substitute for isoflurane is less than on a minimum alveolar concentration basis. Maintaining median electroencephalographic frequency more appropriately reflects the clinical usage of isoflurane and nitrous oxide than does maintaining minimum alveolar concentration.
Laryngeal Mask Airway in Pediatric Practice
Authors: Lopez-Gil M. , Brimacombe J. , Cebrian J. MD , Arranz J. 
Published: November 2003

Background
A prospective study was conducted to determine the rate of skill acquisition with the laryngeal mask airway in pediatric anesthesiology practice. The aim of the study was to provide information about the amount of supervised training required before satisfactory levels of skill were achieved.

Methods
Eight anesthesia residents in their third year of training with no prior experience using the laryngeal mask airway were observed using the device in 75 pediatric patients each (600 patients in total). Residents were given standardized guidelines for laryngeal mask airway usage in accordance with the manufacturer's recommendations and followed a predetermined protocol for anesthetic management. Induction was achieved with propofol followed by either a propofol infusion or isoflurane and either controlled or spontaneous ventilation as clinically indicated. Predefined major and minor problems were documented during the induction, maintenance, and recovery phases of anesthesia by a randomly selected supervising consultant trained in the study protocol and problem definitions.

Results
The total number of problems was 189 occurring in 121 children. Fifty-five children had one problem, sixty-four children had two problems, and two children had three problems. Of the problems, 77 were major and 112 were minor. The problem rate per patient for overall, major, and minor problems was 31.5%, 12.8%, and 18.7%, respectively. The problem rate comparing the first to last epochs of 15 uses decreased from 62% to 2% for overall problems, 23% to 2% for major problems, and 39 to 1% for minor problems. The residents with the most problems in the final epoch had problem rates of less than 10% after 60 uses. There was a significant decrease in the overall problem rate for induction, maintenance, and recovery (P < 0.05). The major problem rate decreased significantly for induction and maintenance (p < 0.05), but not for recovery. The minor problem rate decreased significantly for induction and recovery (P < 0.05).

Conclusions
This study confirms that there is a rapid improvement in laryngeal mask airway skills when the standard recommended technique is employed and that a low problem rate can be achieved within 75 uses. Pediatric anesthesiologists with problem rates greater than 10% should determine if they are using the device suboptimally.
Remifentanil Versus Alfentanil
Authors: Egan Talmage D. , Minto Charles F. , Hermann David J. , Barr Juliana , Muir Keith T. , Shafer Steven L. 
Published: November 2003

Background
Remifentanil is an esterase-metabolized opioid with a rapid clearance. The aim of this study was to contrast the pharmacokinetics and pharmacodynamics of remifentanil and alfentanil in healthy, adult male volunteers.

Methods
Ten volunteers received infusions of remifentanil and alfentanil on separate study sessions using a randomized, open-label crossover design. Arterial blood samples were analyzed to determine drug blood concentrations. The electroencephalogram was employed as the measure of drug effect. The pharmacokinetics were characterized using a moment analysis, a nonlinear mixed effects model (NONMEM) population analysis, and context-sensitive half-time computer simulations. After processing the raw electroencephalogram to obtain the spectral edge parameter, the pharmacodynamics were characterized using an effect compartment, inhibitory maximum effect model.

Results
Pharmacokinetically, the two drugs are similar in terms of steady-state distribution volume (VD(SS)), but remifentanil's central clearance (CLc)) is substantially greater. The NONMEM analysis population pharmacokinetic parameters for remifentanil include a CLc of 2.9 l x min(-1), a VDss of 21.81, and a terminal half-life of 35.1 min. Corresponding NONMEM parameters for alfentanil are 0.36 l x min(-1), 34.11, and 94.5 min. Pharmacodynamically, the drugs are similar in terms of the time required for equilibration between blood and the effect-site concentrations, as evidenced by a T(12)k(e0) for remifentanil of 0.75 min [corrected] and 0.96 min for alfentanil. However, remifentanil is 19 times more potent than alfentanil, with an effective concentration for 50% maximal effect of 19.9 ng x ml(-1) versus 375.9 ng x ml(-1) for alfentanil.

Conclusions
Compared to alfentanil, the high clearance of remifentanil, combined with its small steady-state distribution volume, results in a rapid decline in blood concentration after termination of an infusion. With the exception of remifentanil's nearly 20-times greater potency (30-times if alfentanil partitioning between whole blood and plasma is considered), the drugs are pharmacodynamically similar.
Pharmacokinetics of Dichloroacetate in Patients Undergoing Liver Transplantation
Authors: Shangraw Robert E. , Fisher Dennis M. 
Published: November 2003

Background
Dichloroacetate (DCA) is an effective alternative to bicarbonate to treat lactic acidosis and stabilize acid-base homeostasis during liver transplantation. Although DCA presumably is metabolized by the liver, the impact of end-stage liver disease and liver transplantation on DCA distribution and elimination is unknown. Therefore, the pharmacokinetics of DCA were determined in patients with end-stage liver disease undergoing orthotopic liver transplantation.

Methods
Thirty-three patients undergoing liver transplantation were given DCA as two 40-mg/kg infusions over 60 min, the first after induction of anesthesia, the second 4 h later. Plasma DCA concentrations were determined by gas chromatography-mass spectroscopy. One- and two-compartment pharmacokinetic models were fitted to DCA concentrations versus time data using a mixed-effects population approach. Various models permitted changes in central compartment volume and/or plasma clearance to account for changes in hepatic mass and function and circulatory status during the paleohepatic, anhepatic, and neohepatic periods.

Results
The optimal model had two compartments. DCA clearance was 0.997, 0.0, and 1.69 ml x kg(-1) x min(-1) during the paleohepatic, anhepatic, and neohepatic periods, respectively (P < 0.05). Interindividual variability in central compartment volume differed during the paleohepatic and neohepatic periods. There was no apparent influence of blood or fluid requirements during surgery on DCA clearance or volume of distribution.

Conclusions
Absence of DCA clearance during the anhepatic period indicates that DCA is metabolized exclusively by the liver. Differences in interindividual variability in central compartment volume during the paleohepatic and neohepatic periods possibly result from physiologic changes during surgery. Finally, the results indicate that the newly transplanted liver eliminates DCA better than the native liver.
Anesthetic Potency of Remifentanil in Dogs
Authors: Michelsen Luis G. , Salmenpera Markku , Hug Jr. , Szlam Fania , VanderMeer Dirk 
Published: November 2003

Background
Remifentanil is an opioid that is rapidly inactivated by esterases in blood and tissues. This study examined the anesthetic potency and efficacy of remifentanil in terms of its reduction of enflurane minimum alveolar concentration (MAC) in dogs.

Methods
Twenty-five dogs were anesthetized with enflurane. One group received incremental infusion rates of remifentanil from 0.055 to 5.5 micrograms x kg(-1). A second group received constant rate infusions of remifentanil of 1.0 micrograms x kg(-1) x min(-1) for 6-8 h. Enflurane MAC was measured before, hourly during remifentanil infusion, and at the end of the experiment after naloxone administration. A third group received alternating infusions of 0.5 and 1.0 micrograms x kg(-1) x min(-1) with MAC determinations made 30 min after each change in the infusion rate. Heart rate, mean arterial pressure, and remifentanil blood concentrations were measured during MAC determinations.

Results
Enflurane MAC was reduced up to a maximum of 63 +/- 10.4% (mean +/- SD) in a dose-dependent manner by remifentanil infusion. The dose producing a 50% reduction in the enflurane MAC was calculated as 0.72 micrograms x kg(-1)x min(-1) and the corresponding blood concentration was calculated as 9.2 ng/ml. Enflurane MAC reduction remained stable during continuous, constant rate infusions for periods of 6-8 h without any signs of tolerance. Recovery of enflurane MAC to baseline occurred in 30 min (earliest measurement) after stopping the remifentanil infusion.

Conclusions
Remifentanil is equally efficacious and about half as potent as fentanyl, judging from the blood concentrations causing equivalent reductions in enflurane MAC in the dog. The characteristics of MAC reduction are similar to those of other opioids, including the ceiling effect. Recovery from remifentanil anesthesia is much more rapid than for any other opioid studied to date, especially after continuous infusions maintained for 6 or more h.