bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Alcohol as a Standard to Assess the Degree of Impairment Induced by Sedative and Analgesic Drugs Used in Ambulatory Surgery
Authors: Thapar Pankaj , Zacny James P. , Thompson Wesley , Apfelbaum Jeffrey L.
Published: November 2003

Background

There is a need for a standard by which to compare the degree of subjective and behavioral impairment caused by anesthetic drugs, because anesthesiologists may not be able to gauge how extreme or important a statistically significant change in psychomotor functioning is. This study examined the psychomotor and subjective effects of alcohol at blood concentrations equal or greater than 0.10% as a standard with which to compare those effects caused by sedative and analgesic agents commonly used in ambulatory surgery.

Methods

Twelve healthy human volunteers (11 men and 1 nonpregnant woman), with an average age of 28 yr (range 24-34 yr) and an average alcohol consumption of four drinks per week, were selected in this institutional review board-approved study. Each subject was exposed to five drug conditions (70 mg/70 kg propofol intravenously, 2 mg/70 kg midazolam intravenously, 50 micrograms/70 kg fentanyl intravenously, 0.8 g/kg alcohol orally, and placebo orally and intravenously) in a double-blind randomized fashion over five weekly sessions. Testing was done at baseline and at different intervals until 240 min after drug administration. Testing included psychomotor performance (Maddox Wing, eye-hand coordination, auditory reaction time test, and digit symbol substitution test), subjective effects (strength of drug effect scale, drug liking scale, and visual analog scale), and short-term memory. Psychomotor performance was used as an index of objective impairment, and mood was used as an index of subjective impairment.

Results

After consumption of the alcoholic beverage, a blood alcohol level of 0.11 +/- 0.003% (mean +/- SE) was obtained at 15 min after injection. The study drugs not only produced statistically significant impairment (i.e., impairment greater than that seen with placebo) but also, at one or more times after injection, produced impairment similar to that observed with alcohol at a blood alcohol concentration of 0.11%. Midazolam produced a similar degree of impairment to that of alcohol for a longer duration than did fentanyl and propofol.

Conclusions

This study provides evidence that degree of impairment caused by sedative and analgesic drugs used in ambulatory surgery is similar to that obtained with a dose of alcohol that produces a blood alcohol concentration of 0.11%. We suggest that anesthesiologists can use alcohol as a standard by which to assess degree of impairment produced by drugs used for sedation/analgesia.
The Catecholamine, Cortisol, and Hemodynamic Responses to Mild Perioperative Hypothermia
Authors: Frank Steven M. , Higgins Michael S. , Breslow Michael J. , Fleisher Lee A. , Gorman Randolph B. , Sitzmann James V. , Raff Hershel , Beattle Charles
Published: November 2003

Background

Unintended hypothermia occurs frequently during surgery and may have adverse effects on the cardiovascular system. Although the mechanisms responsible for the cardiovascular manifestations of hypothermia are unclear, it is possible that they are sympathetically mediated. In this prospective study, relationships between body temperature, the neuroendocrine response, and hemodynamic changes in the perioperative period were examined.

Methods

Seventy-four elderly patients, undergoing abdominal, thoracic, or lower extremity vascular surgical procedures, were randomly assigned to either "routine care" (n = 37) or "forced-air warming" (n = 37) groups. Throughout the intraoperative and early postoperative periods, the routine care group received standard thermal care, and the forced-air warming group received forced-air skin-surface warming. Core temperature, forearm minus fingertip skin-surface temperature gradient, and plasma concentrations of epinephrine, norepinephrine, and cortisol were measured throughout the perioperative period, and the two groups were compared. In addition, heart rate and arterial blood pressure were compared between groups.

Results

The routine care and forced-air warming groups did not differ with regard to age, sex, type of surgical procedures, anesthetic techniques, or postoperative analgesia. Mean core temperature was lower in the routine care group on admission to the postanesthetic care unit (routine care, 35.3 +/- 0.1 degree C; forced-air warming, 36.7 +/- 0.1 degree C; P = 0.0001) and remained lower during the early postoperative period. Forearm minus fingertip skin-surface temperature gradient (an index of peripheral vasoconstriction) was greater in the routine care group in the early postoperative period. The mean norepinephrine concentration (pcg/ml) was greater in the routine care group immediately after surgery (480 +/- 70 vs. 330 +/- 30, P = 0.02) and at 60 min (530 +/- 50 vs. 340 +/- 30, P = 0.002) and 180 min (500 +/- 80 vs. 320 +/- 30, P = 0.004) postoperatively. Mean epinephrine concentrations were not significantly different between groups. Mean cortisol concentrations were increased in both groups during the early postoperative period (P < 0.01), but the differences between groups were not significant. Systolic, mean, and diastolic arterial blood pressures were significantly higher in the routine care group.

Conclusions

Compared with patients in the forced-air warming group, patients receiving routine thermal care had lower core temperatures, a greater degree of peripheral vasoconstriction, higher norepinephrine concentrations, and higher arterial blood pressures in the early postoperative period. These findings suggest a possible mechanism for hypothermia-related cardiovascular morbidity in the perioperative period.
Analysis of Strategies to Decrease Postanesthesia Care Unit Costs
Authors: Dexter Franklin , Tinker John H.
Published: November 2003

Background

The goal of this study was to identify interventions that anesthesiologists can make to decrease total costs of a postanesthesia care unit (PACU).

Methods

Data were collected retrospectively from patients who underwent ambulatory surgery at our tertiary care center.

Results

Supplies and medications accounted for only 2% of PACU charges. Personnel costs, which depend on the peak number of patients in the PACU, accounted for almost all PACU costs. If nausea and vomiting could have been eliminated in each patient who suffered this complication, without causing sedation, the total time to discharge for all patients would have been decreased by less than 4.8% (95% confidence interval < 7.3%). Arrival rates to and times to discharge from the PACU followed triangular and log-normal distributions, respectively. Computer simulations, using published times to discharge for drugs with "faster recovery," such as propofol, showed that the use of these drugs would only decrease PACU costs if operating rooms were consistently scheduled to run later each day. Such earlier discharge also might be beneficial if used at night, but only if the PACU could close after a single patient leaves. However, reasonably achievable decreases in the times to discharge for all patients undergoing general anesthesia are unlikely to substantively decrease PACU costs. In contrast, arranging an operating room schedule to optimize admission rates would greatly affect the number of PACU nurses needed.

Conclusions

Anesthesiologists have little control over PACU economics via choice of anesthetic drugs. The major determinant of PACU costs is the distribution of admissions.
Sensitization of Spinal Neurons by Non-noxious Stimuli in the Awake but Not Anesthetized State
Authors: Herrero Juan F. , Headley Max P.
Published: November 2003

Background

The observation that peripheral trauma causes enhanced spinal neuronal excitability has provided the scientific rationale for the concept of "pre-emptive analgesia." The premise has been that only noxious stimuli cause sensitization in sensory pathways, but this premise has not been tested in the conscious state.

Methods

Responses of single spinal neurons were recorded in instrumented sheep that were untrained and free from drugs or recent surgery, in either fully conscious or halothane-anesthetized states. Receptive field (RF) size was measured before and after non-noxious mechanical conditioning stimulation.

Results

Noxious conditioning stimuli in anesthetized sheep caused enlargement of RF areas, as expected. Conditioning with nonpainful scratching or other stimuli was without effect in anesthetized animals; in marked contrast, it caused enlargement of RF size in conscious animals, in which 29 of 33 wide dynamic range units but only 1 of 12 low-threshold mechanoreceptive neurons were affected.

Conclusions

Sensitization of spinal sensory neurons evidently is a process that is not restricted to pathologic pain states but rather that occurs under normal physiologic conditions independent of painful stimuli. The significance of such sensitization processes therefore needs reevaluation. The sensitization triggered by non-nociceptive afferents is likely to be opioid-resistant and therefore may contribute to the rather disappointing results seen in several clinical trials of "pre-emptive analgesia."
General Anesthetics Modify the Kinetics of Nicotinic Acetylcholine Receptor Desensitization at Clinically Relevant Concentrations
Authors: Raines Douglas E. , Rankin Saffron E. , Miller Keith W.
Published: November 2003

Background

General anesthetics are thought to induce anesthesia through their actions on ligand-gated ion channels. One such channel, the nicotinic acetylcholine receptor (nAcChoR), can be found in different subtypes in the central nervous system and at the periphery in the neuromuscular junction. The latter subtype of the nAcChoR is a useful model for examining interactions between general anesthetics and ligand-gated ion channels, because it can be isolated and purified in sufficient quantities to allow for biophysical and biochemical studies. This study examines the actions of general anesthetics on agonist-induced conversion of the nAcChoR to inactive desensitized conformational states.

Methods

Nicotinic acetylcholine receptor membranes were purified from the electric organ of Torpedo nobiliana. Agonist-induced desensitization was characterized from the time-dependent increase in fluorescence intensity that results from the binding of the fluorescent acetylcholine analog, Dns-C6-Cho, to the nAcChoR.

Results

Mixing Dns-C6-Cho with nAcChoR-rich membranes results in an increase in fluorescence that is characterized by four rate processes. Concentrations of isoflurane and butanol, which range from subclinical to toxic increase the rates of the third and fourth components of fluorescence, corresponding to fast and slow desensitization, respectively. At concentrations that are twice their EC50s for anesthesia, isoflurane, butanol, chloroform, methanol, and cyclopentanemethanol increase the apparent rates of fast and slow desensitization by an average of 92 +/- 22% and 108 +/- 22%, respectively.

Conclusions

The concentration range over which general anesthetics modify the kinetics of nAcChoR desensitization is similar to those reported for anesthetic actions on the GABAA receptor. Thus, the nAcChoR, like other members of this superfamily, is a sensitive target of general anesthetics.
Phase I Safety Assessment of Intrathecal Neostigmine Methylsulfate in Humans
Authors: Hood David D. , Eisenach James C. , Tuttle Robin
Published: November 2003

Background

In dogs, sheep, and rats, spinal neostigmine produces analgesia alone and enhances analgesia from alpha 2-adrenergic agonists. This study assesses side effects and analgesia from intrathecal neostigmine in healthy volunteers.

Methods

After institutional review board approval and informed consent, 28 healthy volunteers were studied. The first 14 volunteers received neostigmine (50-750 micrograms) through a #19.5 spinal needle followed by insertion of a spinal catheter. The remaining 14 volunteers received neostigmine through a #25 or #27 spinal needle without a catheter. Safety measurements included blood pressure, heart rate, oxyhemoglobin saturation, end-tidal carbon dioxide, neurologic evaluation, and computer tests of vigilance and memory. Analgesia in response to ice water immersion was measured.

Results

Neostigmine (50 micrograms) through the #19.5 needle did not affect any measured variable. Neostigmine (150 micrograms) caused mild nausea, and 500-750 micrograms caused severe nausea and vomiting. Neostigmine (150-750 micrograms) produced subjective leg weakness, decreased deep tendon reflexes, and sedation. The 750-micrograms dose was associated with anxiety, increased blood pressure and heart rate, and decreased end-tidal carbon dioxide. Neostigmine (100-200 micrograms) in saline, injected through a #25 or #27 needle, caused protracted, severe nausea, and vomiting. This did not occur when dextrose was added to neostigmine. Neostigmine by either method of administration reduced visual analog pain scores to immersion of the foot in ice water.

Conclusions

The incidence and severity of these adverse events from intrathecal neostigmine appears to be affected by dose, method of administration, and baricity of solution. These effects in humans are consistent with studies in animals. Because no unexpected or dangerous side effects occurred, cautious examination of intrathecal neostigmine alone and in combination with other agents for analgesia is warranted.
An Evaluation of the Effect of Anesthetic Technique on Reproductive Success after Laparoscopic Pronuclear Stage Transfer
Authors: Vincent Robert D. , Syrop Craig H. , Van Voorhis Bradley J. , Chestnut David H. , Sparks Amy E. T. , McGrath Joan M. , Choi Won W. , Bates James N. , Penning Donald H.
Published: November 2003

Background

Laparoscopic pronuclear stage transfer (PROST) is the preferred method of embryo transfer after in vitro fertilization in many infertility programs. There are scant data to recommend the use or avoidance of any particular anesthetic agent for use in women undergoing this procedure. The authors hypothesized that propofol would be an ideal anesthetic for laparoscopic PROST because of its characteristic favorable recovery profile that includes minimal sedation and a low incidence of postoperative nausea and vomiting. The purpose of the study was to compare propofol and isoflurance with respect to postanesthetic recovery and pregnancy outcomes after laparoscopic PROST.

Methods

One hundred twelve women scheduled for laparoscopic PROST were randomized to receive either propofol/nitrous oxide or isoflurane/nitrous oxide for maintenance of anesthesia.

Results

Visual analog scale scores for sedation were lower in the propofol group than in the isoflurance group at all measurements between 30 min and 3 h after surgery. More women experienced emesis and were given an antiemetic during recovery in the isoflurance group than in the propofol group. However, the percentage of pregnancies with evidence of fetal cardiac activity was 54% in the isoflurane group compared with only 30% in the propofol group (P = 0.023). Also, the ongoing pregnancy rate was greater in the isoflurane group than in the propofol group (54% vs. 29%, P = 0.014).

Conclusions

Propofol/nitrous oxide anesthesia was associated with lower clinical and ongoing pregnancy rates compared with isoflurane/nitrous oxide anesthesia.
Distribution of Cerebral Blood Flow during Anesthesia with Isoflurane or Halothane in Humans
Authors: Reinstrup Peter , Ryding Erik , Algotsson Lars , Messeter Kenneth , Asgeirsson Bogi , Uski Tore
Published: November 2003

Background

Halothane and isoflurane have been shown to induce disparate effects on different brain structures in animals. In humans, various methods for measuring cerebral blood flow (CBF) have produced results compatible with a redistribution of CBF toward deep brain structures during isoflurane anesthesia in humans. This study was undertaken to examine the effects of halothane and isoflurance on the distribution of CBF.

Methods

Twenty ASA physical status patients (four groups, five in each) anesthetized with either isoflurane or halothane (1 MAC) during normo- or hypocapnia (PaCO2 5.6 or 4.2 kPa (42 or 32 mmHg)) were investigated with a two-dimensional CBF measurement (CBFxenon, intravenous 133xenon washout technique) and a three-dimensional method for measurement of the regional CBF (rCBF) distribution with single photon emission computer-aided tomography (SPECT; 99mTc-HMPAO). In the presentation of SPECT data, the mean CBF of the brain was defined as 100%, and all relative flow values are related to this value.

Results

The mean CBFxenon level was significantly influenced by the PaCO2 as well as by the anesthetic used. At normocapnia, patients anesthetized with halothane had a mean CBFxenon of 40 +/- 3 (SE) ISI units. With isoflurane, the flow was significantly (P < 0.01, 33 +/- 3 ISI units) less than with halothane. Hypocapnia decreased mean CBFxenon (P < 0.0001) during both anesthetics (halothane 24 +/- 3, isoflurane 13 +/- 2 ISI units). The effects on CBFxenon, between the anesthetics, differed significantly (P < 0.01) also during hypocapnia. There were significant differences in rCBF distribution measured between the two anesthetics (P < 0.05). During isoflurane anesthesia, there was a relative increase in flow values in subcortical regions (thalamus and basal ganglia) to 10-15%, and in pons to 7-10% above average. Halothane, in contrast, induced the highest relative flow levels in the occipital lobes, which increased by approximately 10% above average. The rCBF level was increased approximately 10% in cerebellum with both anesthetics. Changes in PaCO2 did not alter the rCBF distribution significantly.

Conclusions

There is a difference in the human rCBF distribution between halothane and isoflurane with higher relative flows in subcortical regions during isoflurane anesthesia. However, despite this redistribution, isoflurane anesthesia resulted in a lower mean CBFxenon than did anesthesia with halothane.
Death and Other Complications of Emergency Airway Management in Critically Ill Adults
Authors: Schwartz David E. , Matthay Michael A. , Cohen Neal H.
Published: November 2003

Background

Hospitalized patients outside of the operating room frequently require emergency airway management. This study investigates complications of emergency airway management in critically ill adults, including: (1) the incidence of difficult and failed intubation; (2) the frequency of esophageal intubation; (3) the incidence of pneumothorax and pulmonary aspiration; (4) the hemodynamic consequences of emergent intubation, including death, during and immediately following intubation; and (5) the relationship, if any, between the occurrence of complications and supervision of the intubation by an attending physician.

Methods

Data were collected on consecutive tracheal intubations carried out by the intensive care unit team over a 10-month period. Non-anesthesia residents were supervised by anesthesia residents, critical care attending physicians, or anesthesia attending physicians.

Results

Two hundred ninety-seven consecutive intubations were carried out in 238 adult patients. Translaryngeal tracheal intubation was accomplished in all patients. Intubation was difficult in 8% of cases (requiring more than two attempts at laryngoscopy by a physician skilled in airway management). Esophageal intubation occurred in 25 (8%) of the attempts but all were recognized before any adverse sequelae resulted. New infiltrates suggestive of pulmonary aspiration were present on chest radiography after 4% of intubations. Seven patients (3%) died during or within 30 min of the procedure. Five of the seven patients had systemic hypotension (systolic blood pressure < or = 90 mmHg), and four of the five were receiving vasopressors to support systolic blood pressure. Patients with systolic hypotension were more likely to die after intubation than were normotensive patients (P < 0.001). There was no relationship between supervision by an attending physician and the occurrence of complications.

Conclusions

In critically ill patients, emergency tracheal intubation is associated with a significant frequency of major complications. In this study, complications were not increased when intubations were accomplished without the supervision of an attending physician as long as the intubation was carried out or supervised by an individual skilled in airway management. Mortality associated with emergent tracheal intubation is highest in patients who are hemodynamically unstable and receiving vasopressor therapy before intubation.
The Dose-Response Relationship of Tranexamic Acid
Authors: Horrow Jan C. , Van Riper Daniel F. , Strong Michael D. , Grunewald Karl E. , Parmet Jonathan L.
Published: November 2003

Background

Prophylactic administration of the antifibrinolytic drug tranexamic acid decreases bleeding and transfusions after cardiac operations. However, the best dose of tranexamic acid for this purpose remains unknown. This study explored the dose-response relationship of tranexamic acid for hemostatic efficacy after cardiac operation.

Methods

In prospective, randomized, double-blinded fashion, 148 patients undergoing cardiac operation with extracorporeal circulation were divided into six groups: a placebo group and five groups receiving tranexamic acid in loading doses before incision (range 2.5 to 40 mg.kg-1) and one-tenth the loading dose hourly for 12 h. The mass of blood collected by chest tubes over 12 h represented blood loss. Allogeneic transfusions within 12 h and within 5 d of surgery were tallied.

Results

The six groups presented similar demographics. Patients receiving placebo had increased postoperative D-dimer concentration compared to groups receiving tranexamic acid. Patients receiving at least 10 mg.kg-1 tranexamic acid followed by 1 mg.kg-1.h-1 bled significantly less (365, 344, and 369 g.12 h-1, respectively, for those three groups) compared with patients who received placebo (552 g, P < 0.05). Tranexamic dose did not affect transfusions. Only initial hematocrit affected whether a patient received an allogeneic transfusion within 5 days of operation (odds ratio 2.08 for each 3% absolute decrease in hematocrit).

Conclusions

Prophylactic tranexamic acid, 10 mg.kg-1 followed by 1 mg.kg-1.h-1, decreases bleeding after extracorporeal circulation. Larger doses do not provide additional hemostatic benefit.
The Magnitude and Time Course of Vecuronium Potentiation by Desflurane Versus Isoflurane
Authors: Wright Peter M.C. , Hart Paul , Lau Marie , Brown Ronald , Sharma Manohar L. , Gruenke Larry , Fisher Dennis M.
Published: November 2003

Background

Preliminary studies suggest that desflurane and isoflurane potentiate the action of muscle relaxants equally. However, variability between subjects may confound these comparisons. A crossover study was performed in volunteers on the ability of desflurane and isoflurane to potentiate the neuromuscular effect of vecuronium, to influence its duration of action, and on the magnitude and time course of reversal of potentiation when anesthesia was withdrawn.

Methods

Adductor pollicis twitch tension was monitored in 16 volunteers given 1.25 MAC desflurane on one occasion, and 1.25 MAC isoflurane on another. In eight subjects, vecuronium bolus dose potency was determined using a two-dose dose-response technique; the vecuronium infusion dose requirement to achieve 85% twitch depression also was determined. Also in these subjects, the magnitude and time course of spontaneous neuromuscular recovery were determined when the anesthetic was withdrawn while maintaining a constant vecuronium infusion. In the other eight subjects, the time course of action of 100 micrograms/kg vecuronium was determined.

Results

Vecuronium's ED50 and infusion requirement to maintain 85% twitch depression were 20% less during desflurane, compared to isoflurane, anesthesia; vecuronium plasma clearance was similar during the two anesthetics. After 100 micrograms/kg vecuronium, onset was faster and recovery was longer during desflurane anesthesia. When the end-tidal anesthetic concentration was abruptly reduced from 1.25 to 0.75 MAC, twitch tension increased similarly (approximately 15% of control), and time for the twitch tension to reach 90% of the final change was similar (approximately 30 min) with both anesthetics. Decreasing anesthetic concentration from 0.75 to 0.25 MAC increased twitch tension by 46 +/- 10% and 25 +/- 7% of control (mean +/- SD, P < 0.001) with desflurane and isoflurane, respectively; 90% response times for these changes were 31 +/- 10 min and 18 +/- 7 min (P < 0.05), respectively.

Conclusions

Desflurane potentiates the effect of vecuronium approximately 20% more than does an equipotent dose of isoflurane.
In Vitro Effects of Fentanyl, Methohexital, and Thiopental on Brain Endothelial Permeability
Authors: Fischer S. , Renz D. , Schaper W. , Karliczek G. F.
Published: November 2003

Background

The use of anesthetics can lead to changes of the permeability of the blood-brain barrier (BBB). To eliminate those factors, such as varying hemodynamic effects that are associated with anesthesia, an in vitro model of the BBB consisting of brain microvascular endothelial cells (BMEC) was used to study the direct effects of the opiate, fentanyl, and the barbiturates methohexital and thiopental, which are widely used in the clinical setting, on the permeability of confluent monolayers.

Methods

BMEC isolated from porcine brains were grown to confluence on collagen-coated polycarbonate membranes, which were placed into 24 well dishes, thus forming a two-compartment chamber. The permeability of the BMEC monolayer to ions--determined by measurements of the transendothelial resistance (TER)--the passage of sucrose, Evans Blue albumin (EBA), and alpha-aminoisobutyric acid (AIB) across the BMEC monolayer were assessed in the presence and absence of fentanyl (25-100 ng/ml), methohexital (10-50 micrograms/ml), and thiopental (25-100 micrograms/ml).

Results

The permeability of cultured BMEC to the tracers used increased significantly after exposure of the monolayer to arabinose and after removal of calcium ions. Fentanyl, methohexital, and thiopental did not change the permeability of the cell monolayer to ions, sucrose, albumin, and AIB. Only thiopental at the concentration of 100 micrograms/ml increased the flux of AIB.

Conclusions

At the concentrations tested, there is little evidence of changes in the permeability of the in vitro BBB caused by fentanyl, methohexital, and thiopental regarding the para- and transcellular route of ions, sucrose, and albumin. Only thiopental at a concentration of 100 micrograms/ml increased the passage of AIB across the BMEC monolayer.
Bupivacaine Transfer across the Human Term Placenta
Authors: Johnson Raymond F. , Herman Norman , Arney Timothy L. , Gonzalez Herbert , Johnson Vernetta H. , Downing John W.
Published: November 2003

Background

Bupivacaine is widely used for obstetric analgesia, yet published information on the mechanism of human placental bupivacaine transfer is sparse. The dual perfused human placental model was used to elucidate the factors governing the placental transfer of bupivacaine.

Methods

Bupivacaine transfer was studied using the recirculating (closed) model and the single pass (open) model. Single placental cotyledons were perfused with either heparinized Krebs-Ringer's buffer (KRB) supplemented with human albumin (fetal and maternal circuits) or 100% fresh frozen plasma (maternal circuit) to control the bupivacaine protein binding in those circuits. In the open model, bupivacaine clearance was compared before and after being subjected to either increasing concentrations of bupivacaine or its structural analog, mepivacaine.

Results

For those studies in which the maternal and fetal protein binding was equal, the maternal to fetal (M-->F) transfer was significantly greater (P < 0.05) than that in the fetal to maternal (F-->M) direction. When the perfusates were modified to simulate actual in vivo plasma protein concentrations, bupivacaine transfer was shown to be related to the degree of protein binding found in the two circuits. In the open studies, bupivacaine transfer was similar at all concentrations investigated, unaffected by mepivacaine, and related to the pH of the fetal perfusate. A concentration effect was seen within the placental tissue at the end of the experiment.

Conclusions

Bupivacaine placental transfer characteristics suggest passive diffusion rather than active drug transport and appear to be influenced by the maternal and fetal plasma protein binding, fetal pH, and placental uptake.
Anesthetics and Automaticity of Dominant and Latent Atrial Pacemakers in Chronically Instrumented Dogs
Authors: Vicenzi Martin N. , Woehlck Harvey J. , Bajic Jurica , Sokolyk Stephen M. , Bosnjak Zeljko J. , Atlee John L.
Published: November 2003

Background

Management of patients with sinus node dysfunction must consider the stability of subsidiary pacemakers during anesthesia and treatment with antimuscarinic or sympathomimetic drugs. Baroreflex regulation of atrial pacemaker function is known to contribute to the interactions between inhalation anesthetics and catecholamines. Sinoatrial (SA) node excision can be a model for intrinsic SA node dysfunction. Subsidiary atrial pacemakers are expected to emerge after SA node excision, but they may respond differently to humoral and neural modulation. Isolated and combined effects of epinephrine and methylatropine should help characterize subsidiary pacemaker function during anesthesia with halothane, isoflurane, and enflurane.

Methods

In eight dogs, SA nodes were excised and epicardial electrodes implanted at the atrial appendages, the His bundle, and along the sulcus terminalis. Spontaneous pacemaker automaticity and subsidiary atrial pacemaker recovery time were measured in the conscious state, in the presence of methylatropine, with 1 and 2 micrograms.kg-1.min-1 epinephrine and during 1.25 and 2 MAC halothane, isoflurane, and enflurane.

Results

After SA node excision, a stable and regular subsidiary atrial pacemaker rhythm emerged. Each anesthetic prolonged subsidiary atrial pacemaker recovery times. This prolongation was greater in the presence of methylatropine. Without methylatropine, isoflurane and enflurane, but not halothane, further enhanced the baroreflex-mediated negative chronotropic effects of epinephrine, whereas with methylatropine, each anesthetic reduced the direct positive chronotropic effects of epinephrine.

Conclusions

Halothane, isoflurane, and enflurane have significant depressant effects on the spontaneous and epinephrine-altered automaticity of subsidiary atrial pacemakers. Depression of subsidiary atrial pacemaker automaticity was most apparent in dogs with muscarinic blockade.
Halothane and Isoflurane Decrease the Open State Probability of Potassium sup + Channels in Dog Cerebral Arterial Muscle Cells
Authors: Eskinder Hanna , Gebremedhin Debebe , Lee Joseph G. , Rusch Nancy J. , Supan Franjo D. , Kampine John P. , Bosnjak Zeljko J.
Published: November 2003

Background

Both halothane and isoflurane evoke cerebral vasodilation. One of the potential mechanisms for arterial vasodilation is enhanced K+ efflux resulting from an increased opening frequency of membrane K+ channels. The current study was designed to determine the effects of volatile anesthetics on K+ channel current in single vascular smooth muscle cells isolated from dog cerebral arteries.

Methods

Patch clamp recording techniques were used to investigate the effects of volatile anesthetics on macroscopic and microscopic K+ channel currents.

Results

In the whole-cell patch-clamp mode, in cells dialyzed with pipette solution containing 2.5 mM EGTA and 1.8 mM CaCl2, depolarizing pulses from -60 to +60 mV elicited an outward K+ current that was blocked 65 +/- 5% by 3 mM tetraethylammonium (TEA). Halothane (0.4 and 0.9 mM) depressed the amplitude of this current by 18 +/- 4% and 34 +/- 6%, respectively. When 10 mM EGTA was used in the pipette solution to strongly buffer intracellular free Ca2+, an outward K+ current insensitive to 3 mM TEA was elicited. This K+ current, which was reduced 51 +/- 4% by 1 mM 4-aminopyridine, was also depressed by 17 +/- 5% and 29 +/- 7% with application of 0.4 and 0.9 mM halothane, respectively. In cell-attached patches using 145 mM KCl in the pipette solution and 5.2 mM KCl in the bath, the unitary conductance of the predominant channel type detected was 99 pS. External application of TEA (0.1 to 3 mM) reduced the unitary current amplitude of the 99 pS K+ channel in a concentration-dependent manner. The open state probability of this 99 pS K+ channel was increased by 1 microM Ca2+ ionophore (A23187). These findings indicate that the 99 pS channel measured in cell-attached patches was a TEA-sensitive, Ca(2+)-activated K+ channel. Halothane and isoflurane reversibly decreased the open state probability (NPo), mean open time, and frequency of opening of this 99 pS K+ channel without affecting single channel amplitude or the slope of the current-voltage relationship.

Conclusions

Halothane and isoflurane suppress the activity of K+ channels in canine cerebral arterial cells. These results suggest that mechanisms other than K+ channel opening likely mediate volatile anesthetic-induced vasodilation.
Anesthetics Affect the Uptake but Not the Depolarization-evoked Release of GABA in Rat Striatal Synaptosomes
Authors: Mantz Jean , Lecharny Jean-Baptiste , Laudenbach Vincent , Henzel Danielle , Peytavin Gilles , Desmonts Jean-Marie
Published: November 2003

Background

Numerous classes of anesthetic agents have been shown to enhance the effects mediated by the postsynaptic gamma-aminobutyric acid A (GABAA) receptor-coupled chloride channel in the mammalian central nervous system. However, presynaptic actions of anesthetics potentially relevant to clinical anesthesia remain to be clarified. Therefore, in this study, the effects of intravenous and volatile anesthetics on both the uptake and the depolarization-evoked release of GABA in the rat striatum were investigated.

Methods

Assay for specific GABA uptake was performed by measuring the radioactivity incorporated in purified striatal synaptosomes incubated with 3H-GABA (20 nM, 5 min, 37 degrees C) and increasing concentrations of anesthetics in either the presence or the absence of nipecotic acid (1 mM, a specific GABA uptake inhibitor). Assay for GABA release consisted of superfusing 3H-GABA preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml.min-1, 37 degrees C) and measuring the radioactivity obtained from 0.5 ml fractions over 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of either KCl alone (9 mM, 15 mM) or with various concentrations of anesthetics (5 min), and finally, with no pharmacologic stimulation (5 min). The following anesthetic agents were tested: propofol, etomidate, thiopental, ketamine, halothane, enflurane, isoflurane, and clonidine.

Results

More than 95% of 3H-GABA uptake was blocked by a 10(-3)-M concentration of nipecotic acid. Propofol, etomidate, thiopental, and ketamine induced a dose-related, reversible, noncompetitive, inhibition of 3H-GABA uptake: IC50 = 4.6 +/- 0.3 x 10(-5) M, 5.8 +/- 0.3 x 10(-5) M, 2.1 +/- 0.4 x 10(-3) M, and 4.9 +/- 0.5 x 10(-4) M for propofol, etomidate, thiopental, and ketamine, respectively. Volatile agents and clonidine had no significant effect, even when used at concentrations greater than those used clinically. KCl application induced a significant, calcium-dependent, concentration-related, increase from basal 3H-GABA release, +34 +/- 10% (P < 0.01) and +61 +/- 13% (P < 0.001), respectively, for 9 mM and 15 mM KCl. The release of 3H-GABA elicited by KCl was not affected by any of the anesthetic agents tested.

Conclusions

These results indicate that most of the intravenous but not the volatile anesthetics inhibit the specific high-affinity 3H-GABA uptake process in vitro in striatal nerve terminals. However, this action was observed at clinically relevant concentrations only for propofol and etomidate. In contrast, the depolarization-evoked 3H-GABA release was not affected by anesthetics. Together, these data suggest that inhibition of GABA uptake, which results in synaptic GABA accumulation, might contribute to propofol and etomidate anesthesia.
Hyperglycemia during Hypothermic Canine Cardiopulmonary Bypass Increases Cerebral Lactate
Authors: Feerick Alan E. , Johnston William E. , Jenkins Larry W. , Lin Cheng Y. , Mackay Jonathan H. , Prough Donald S.
Published: November 2003

Background

Hyperglycemia frequently occurs during cardiopulmonary bypass (CPB), although its direct effects on cerebral perfusion and metabolism are not known. Using a canine model of hypothermic CPB, we tested whether hyperglycemia alters cerebral blood flow and metabolism and cerebral energy charge.

Methods

Twenty anesthetized dogs were randomized into hyperglycemic (n = 10) and normoglycemic (n = 10) groups. The hyperglycemic group received an infusion of D50W, and the normoglycemic animals received an equal volume of 0.9% NaCl. Both groups underwent 120 min of hypothermic (28 degrees C) CPB using membrane oxygenators, followed by rewarming and termination of CPB. Cerebral blood flow (radioactive microspheres) and the cerebral metabolic rate for oxygen were measured intermittently during the experiment and brain tissue metabolites were obtained after bypass.

Results

Before CPB, the glucose-treated animals had higher serum glucose levels (534 +/- 12 mg/dL; mean +/- SE) than controls (103 +/- 4 mg/dL; P < 0.05), and this difference was maintained throughout the study. Cerebral blood flow and metabolism did not differ between groups at any time during the experiment. Sagittal sinus pressure was comparable between groups throughout CPB. Tissue high-energy phosphates and water contents were similar after CPB, although cerebral lactate levels were greater in hyperglycemic (37.2 +/- 5.7 mumol/g) than normoglycemic animals (19.7 +/- 3.7 mumol/g; P < 0.05). After CPB, pH values of cerebrospinal fluid for normoglycemic (7.33 +/- 0.01) and hyperglycemic (7.34 +/- 0.01) groups were similar.

Conclusions

Hyperglycemia during CPB significantly increases cerebral lactate levels without adversely affecting cerebral blood flow and metabolism, cerebrospinal fluid pH, or cerebral energy charge.
Coronary Vasodilation by Isoflurane
Authors: Crystal George J. , Czinn Edward A. , Silver Jeffrey M. , Salem Ramez M.
Published: November 2003

Background

Under certain circumstances, isoflurane is associated with coronary artery vasodilation. The objective of the current study was to ascertain whether the rate of administration of isoflurane influences its vasodilating effect in the coronary circulation.

Methods

Seven open-chest dogs anesthetized with fentanyl and midazolam were studied. The left anterior descending coronary artery was perfused via either of two pressurized (80 mmHg) reservoirs; reservoir 1 (control) was supplied with arterial blood free of isoflurane, and reservoir 2 was supplied with blood from an extracorporeal oxygenator, which was provided with 95% O2/5% CO2 gas that passed through calibrated vaporizer. Coronary blood flow (CBF) was measured with Doppler flow transducer. In each dog, isoflurane was administered according to two protocols; abrupt (isoflurane-A) or gradual (isoflurane-G). In isoflurane-A, the left anterior descending coronary artery was switched from reservoir 1 to reservoir 2 after the latter was filled with blood previously equilibrated with 1.4% (1 MAC) isoflurane. In isoflurane-G, the left anterior descending coronary artery was switched to reservoir 2 with vaporizer set at 0% isoflurane; then the vaporizer was adjusted to 1.4% isoflurane, which produced a gradual increase in isoflurane concentration within reservoir 2 that reached a level equivalent to that in isoflurane-A (as evaluated by gas chromatography) by 30 min. CBF during maximally dilating, intracoronary infusion of adenosine served as a reference to assess effects of isoflurane.

Results

Isoflurane-A caused marked increases in CBF, which, at constant perfusion pressure, reflected pronounced reductions in vascular resistance. These increases in CBF were 80% of those with adenosine. Although isoflurane-G also caused increases in CBF, the increases were only 45% of those caused by isoflurane-A.

Conclusions

The current findings demonstrate that the extent of coronary vasodilation by isoflurane was not dependent only on its blood concentration but also on the rate at which this blood concentration was achieved; a gradual increase in blood concentration blunted the vasodilator effect. Differences in the rate of administration of isoflurane likely contributed to its widely variable coronary vasodilating effects in previous studies.
Cerebrovascular Carbon Dioxide Reactivity in Carotid Artery Disease
Authors: Thiel A. , Zickmann B. , Stertmann W. A. , Wyderka T. , Hempelmann G.
Published: November 2003

Background

In patients with carotid artery disease, poor intracerebral collateralization is reflected by impaired cerebrovascular reactivity to carbon dioxide inhalation, which will improve after endarterectomy. The relationship between preoperative reactivity to carbon dioxide using transcranial Doppler sonography (TCD) and intraoperative changes of somatosensory evoked potentials (SEP) and TCD parameters were investigated.

Methods

In 94 patients, preoperative carbon dioxide reactivity was examined and defined impaired if mean blood flow velocity in the middle cerebral artery (Vm-MCA) increased less than 1.5% mmHg during carbon dioxide challenge. Patients then underwent 100 carotid operations under general anesthesia with both SEP and TCD monitoring. Shunts were placed if SEP amplitude decreased to less then 50% of control or central conduction time increased by 20% after clamping (critical SEP changes). TCD changes were defined as critical in case of a postclamping/preclamping Vm-MCA ratio < or = 0.4. The incidence of critical SEP and TCD changes was compared to preoperative carbon dioxide testing using Fisher's exact test with P < 0.05 considered significant. Postoperatively, neurologic state and carbon dioxide responsiveness were re-examined.

Results

Twelve patients showed impaired preoperative carbon dioxide reactivity on the side of operation, which improved markedly after surgery. The incidence of critical SEP changes in these cases (8.3%) was not significantly different from that in the remaining patients (14.8%). Critical SEP changes were significantly correlated with critical TCD changes (P < 0.0001).

Conclusions

Patients with poor carbon dioxide reactivity (preoperative TCD testing) did not have an increased risk of cerebral ischemia during carotid surgery, as assessed by intraoperative SEP recording.
Heat Flow and Distribution during Induction of General Anesthesia
Authors: Matsukawa Takashi , Sessler Daniel I. , Sessler Andrew M. , Schroeder Marc , Ozaki Makoto , Kurz Andrea , Cheng Christi
Published: November 2003

Background

Core hypothermia after induction of general anesthesia results from 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 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.

Methods

Six minimally clothed male volunteers in an approximately 22 degrees C environment were evaluated for 2.5 control hours before induction of general anesthesia and for 3 subsequent hours. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. To separate the effects of redistribution and net heat loss, we multiplied the change in overall heat balance by body weight and the specific heat of humans. The resulting change in mean body temperature was subtracted from the change in distal esophageal (core) temperature, leaving the core hypothermia specifically resulting from redistribution.

Results

Core temperature was nearly constant during the control period but decreased 1.6 +/- 0.3 degree C in the first hour of anesthesia. Redistribution contributed 81% to this initial decrease and required transfer of 46 kcal from the trunk to the extremities. During the subsequent 2 h of anesthesia, core temperature decreased an additional 1.1 +/- 0.3 degree C, with redistribution contributing only 43%. Thus, only 17 kcal was redistributed during the second and third hours of anesthesia. Redistribution therefore contributed 65% to the entire 2.8 +/- 0.5 degree C decrease in core temperature during the 3 h of anesthesia. Proximal extremity heat content decreased slightly after induction of anesthesia, but distal heat content increased markedly. The distal extremities thus contributed most to core cooling. Although the arms constituted only a fifth of extremity mass, redistribution increased arm heat content nearly as much as leg heat content. Distal extremity heat content increased approximately 40 kcal during the first hour of anesthesia and remained elevated for the duration of the study.

Conclusions

The arms and legs are both important components of the peripheral thermal compartment, but distal segments contribute most. Core hypothermia during the first hour after induction resulted largely from redistribution of body heat, and redistribution remained the major cause even after 3 h of anesthesia.
Effects of Hypothermia, Potassium, and Verapamil on the Action Potential Characteristics of Canine Cardiac Purkinje Fibers
Authors: Sprung Juraj , Laszlo Adam , Turner Lawrence , Kampine John , Bosnjak Zeljko
Published: November 2003

Background

Hypothermia may induce hypokalemia and increase intracellular Ca2+ by affecting serum K+ and Ca2+ fluxes across the cell membrane. These ionic alterations may significantly change the electrophysiologic characteristics of the cardiac action potential and may induce cardiac arrhythmias. The current study was undertaken to determine whether electrophysiologic changes in Purkinje fibers induced by hypothermia could be reversed by manipulating the extracellular K+ and transmembrane Ca2+ fluxes by Ca2+ channel blockade with verapamil.

Methods

A conventional microelectrode method was used to determine the effects of hypothermia (32 +/- 0.5 degrees C and 28 +/- 0.5 degrees C) and various external K+ concentrations ([K+]o) (2.3, 3.8, and 6.8 mM) on maximum diastolic potential, maximum rate of phase 0 depolarization (Vmax), and action potential duration (APD) at 50% (APD50) and at 95% (APD95) repolarization in isolated canine cardiac Purkinje fibers. To evaluate the contribution of the slow inward Ca2+ current to action potential changes in hypothermia, the experiments were repeated in the presence of the Ca(2+)-channel antagonist verapamil (1 microM).

Results

Variations of [K+]o induced the expected shifts in maximum diastolic potential, and hypothermia (28 degrees C) induced moderate depolarization, but only when [K+]o was > or = 3.9 mM (P < 0.05). Hypothermia decreased Vmax at all [K+]o studied (P < 0.05). Regardless of the temperature, Vmax was not affected by verapamil when [K+]o was < or = 3.9 mM, but at 6.8 mM [K+]o in hypothermia Vmax was significantly lower in the presence of verapamil. Hypothermia increased both the APD50 and the APD95. The effects of verapamil on APD were temperature and [K+]o dependent; between 37 degrees C and 28 degrees C with 2.3 mM [K+]o in the superfusate, verapamil did not affect APD. At 28 degrees C in the presence of verapamil, the APD50 and APD95 decreased only if the [K+]o was > or = 3.9 mM.

Conclusions

Verapamil and K+ supplementation in hypothermia may exert an antiarrhythmic effect, primarily by reducing the dispersion fo prolonged APD.