bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular and Metabolic Response to Acute Normovolemic Anemia
Authors: Ickx Brigitte E. , Rigolet Michel , Van der Linden Philippe J.
Published: November 2003

Background

The maintenance of adequate tissue oxygenation during acute anemia depends on an increase in both cardiac output and tissue oxygen extraction. This study tested the hypothesis that anesthesia blunts the cardiac output response associated with acute normovolemic hemodilution.

Methods

Forty patients undergoing major abdominal surgery were prospectively randomized to undergo acute normovolemic hemodilution (ANH) either awake (awake group, n = 20) or with fentanyl-nitrous oxide-isoflurane anesthesia (anesthetized group, n = 20). Radial and pulmonary artery catheters were placed in all patients. After hemodynamic measurements were taken, patients in the two groups underwent hemodilution to decrease their hemoglobin concentration from 13 to 8 g/dl. A total of 1,875 +/- 222 ml (mean +/- SD) of blood was collected and simultaneously replaced by the same volume of medium molecular weight hydroxyethylstarch in both groups.

Results

In the awake group, ANH resulted in a significant increase in cardiac index (from 3.1 +/- 0.5 to 4.8 +/- 1.0 l. min-1. m-2) related to both an increase in heart rate and stroke index. Oxygen delivery remained unchanged, but oxygen consumption increased significantly, resulting in an increase in oxygen extraction ratio. In the anesthetized group, ANH resulted in a significantly smaller increase in cardiac index (from 2.3 +/- 0.5 to 3.1 +/- 0.7 l. min-1. m-2) related solely to an increase in stroke index. Oxygen delivery decreased but oxygen consumption was maintained as oxygen extraction increased.

Conclusions

Anesthesia significantly reduces the cardiac output response associated with ANH. This could be related to the effects of the anesthetic drugs on the autonomic and the cardiovascular systems.
Block of Human Heart hH1 Sodium Channels by the Enantiomers of Bupivacaine
Authors: Nau Carla , Wang Sho-Ya , Strichartz Gary R. , Wang Ging Kuo
Published: November 2003

Background

S(-)-bupivacaine reportedly exhibits lower cardiotoxicity but similar local anesthetic potency compared with R(+)-bupivacaine. The bupivacaine binding site in human heart (hH1) Na+ channels has not been studied to date. The authors investigated the interaction of bupivacaine enantiomers with hH1 Na+ channels, assessed the contribution of putatively relevant residues to binding, and compared the intrinsic affinities to another isoform, the rat skeletal muscle (mu1) Na+ channel.

Methods

Human heart and mu1 Na+ channel alpha subunits were transiently expressed in HEK293t cells and investigated during whole cell voltage-clamp conditions. Using site-directed mutagenesis, the authors created point mutations at positions hH1-F1760, hH1-N1765, hH1-Y1767, and hH1-N406 by introducing the positively charged lysine (K) or the negatively charged aspartic acid (D) and studied their influence on state-dependent block by bupivacaine enantiomers.

Results

Inactivated hH1 Na+ channels displayed a weak stereoselectivity with a stereopotency ratio (+/-) of 1.5. In mutations hH1-F1760K and hH1-N1765K, bupivacaine affinity of inactivated channels was reduced by approximately 20- to 40-fold, in mutation hH1-N406K by approximately sevenfold, and in mutations hH1-Y1767K and hH1-Y1767D by approximately twofold to threefold. Changes in recovery of inactivated mutant channels from block paralleled those of inactivated channel affinity. Inactivated hH1 Na+ channels exhibited a slightly higher intrinsic affinity than mu1 Na+ channels.

Conclusions

Differences in bupivacaine stereoselectivity and intrinsic affinity between hH1 and mu1 Na+ channels are small and most likely of minor clinical relevance. Amino acid residues in positions hH1-F1760, hH1-N1765, and hH1-N406 may contribute to binding of bupivacaine enantiomers in hH1 Na+ channels, whereas the role of hH1-Y1767 remains unclear.
Disposition of Bupivacaine and Its Metabolites in the Maternal, Placental, and Fetal Compartments in Rats
Authors: Morishima Hisayo O. , Ishizaki Atsuro , Zhang Yi , Whittington Robert A. , Suckow Raymond F. , Cooper Thomas B.
Published: November 2003

Background

This study was designed to determine the disposition of bupivacaine and its metabolites in the maternal, placental, and fetal compartments, using multiple sampling time points in chronically prepared awake pregnant rats.

Methods

All animals received an intravenous infusion of bupivacaine at a rate of 0.33 mg. kg-1. min-1 over a period of 15 min. The fetuses were delivered either at the end of infusion or at 2 or 4 h after dosing. Maternal and fetal blood and tissue samples were obtained for the assays of bupivacaine and its metabolites using capillary gas chromatography-mass spectrometry.

Results

The elimination half-life of bupivacaine was 37.7 min. The major metabolite was 3'-hydroxybupivacaine. Bupivacaine and 3'-hydroxybupivacaine were present in all samples at the end of administration. The fetal to maternal concentration ratio of bupivacaine in plasma was 0.29, and in the placenta was 0.63. The amnion contained the highest bupivacaine concentration: threefold higher in the maternal and 11-fold higher than in the fetal plasma. At 4 h after dosing, bupivacaine was no longer detectable in any maternal and fetal samples, whereas 3'-hydroxybupivacaine was still present in all tissues except the fetal plasma and heart.

Conclusions

These data indicate that a considerable amount of bupivacaine is taken up by both sides of the placenta, as well as the amnion and myometrium. 3'-Hydroxybupivacaine was present in all tissues except the fetal plasma and heart samples, even after the parent compound became no longer detectable. Whether this slow elimination of 3'-hydroxybupivacaine causes any adverse effects on the fetus-newborn needs to be explored.
Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels
Authors: Yamakura Tomohiro , Harris R. Adron
Published: November 2003

Background

Ligand-gated ion channels are considered to be potential general anesthetic targets. Although most general anesthetics potentiate the function of gamma-aminobutyric acid receptor type A (GABAA), the gaseous anesthetics nitrous oxide and xenon are reported to have little effect on GABAA receptors but inhibit N-methyl-d-aspartate (NMDA) receptors. To define the spectrum of effects of nitrous oxide and xenon on receptors thought to be important in anesthesia, the authors tested these anesthetics on a variety of recombinant brain receptors.

Methods

The glycine, GABAA, GABA receptor type C (GABAC), NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainate, 5-hydroxytryptamine3 (5-HT3), and nicotinic acetylcholine (nACh) receptors were expressed in Xenopus oocytes and effects of nitrous oxide and xenon, and as equipotent concentrations of isoflurane and ethanol, were studied using the two-electrode voltage clamp.

Results

Nitrous oxide (0.58 atmosphere [atm]) and xenon (0.46 atm) exhibited similar effects on various receptors. Glycine and GABAA receptors were potentiated by gaseous anesthetics much less than by isoflurane, whereas nitrous oxide inhibited GABAC receptors. Glutamate receptors were inhibited by gaseous anesthetics more markedly than by isoflurane, but less than by ethanol. NMDA receptors were the most sensitive among glutamate receptors and were inhibited by nitrous oxide by 31%. 5-HT3 receptors were slightly inhibited by nitrous oxide. The nACh receptors were inhibited by gaseous and volatile anesthetics, but ethanol potentiated them. The sensitivity was different between alpha4beta2 and alpha4beta4 nACh receptors; alpha4beta2 receptors were inhibited by nitrous oxide by 39%, whereas alpha4beta4 receptors were inhibited by 7%. The inhibition of NMDA and nACh receptors by nitrous oxide was noncompetitive and was slightly different depending on membrane potentials for NMDA receptors, but not for nACh receptors.

Conclusions

Nitrous oxide and xenon displayed a similar spectrum of receptor actions, but this spectrum is distinct from that of isoflurane or ethanol. These results suggest that NMDA receptors and nACh receptors composed of beta2 subunits are likely targets for nitrous oxide and xenon.
Role of Pump Prime in the Etiology and Pathogenesis of Cardiopulmonary Bypass–associated Acidosis
Authors: Liskaser Frank J. , Bellomo Rinaldo , Hayhoe Matt , Story David , Poustie Stephanie , Smith Benjamin , Letis Angela , Bennett Martin
Published: November 2003

Background

The development of metabolic acidosis during cardiopulmonary bypass (CPB) is well recognized but poorly understood. The authors hypothesized that the delivery of pump prime fluids is primarily responsible for its development. Accordingly, acid-base changes induced by the establishment of CPB were studied using two types of priming fluid (Haemaccel, a polygeline solution, and Ringer's Injection vs. Plasmalyte 148) using quantitative biophysical methods.

Methods

A prospective, double-blind, randomized trial was conducted at a tertiary institution with 22 patients undergoing CPB for coronary artery bypass surgery. Sampling of arterial blood was performed at three time intervals: before CPB (t1), 2 min after initiation of CPB at full flows (t2), and at the end of the case (t3). Measurements of Na+, K+, Mg2+, Cl-, HCO3-, phosphate, Ca2+, albumin, lactate, and arterial blood gases at each collection point were performed. Results were analyzed in a quantitative manner.

Results

Immediately on delivery of pump prime fluids, all patients developed a metabolic acidosis (base excess: 0. 95 mEq/l (t1) to -3.65 mEq/l (t2) (P < 0.001) for Haemaccel-Ringer's and 1.17 mEq/l (t1) to -3.20 mEq/l (t2). The decrease in base excess was the same for both primes (-4.60 vs. -4.37; not significant). However, the mechanism of metabolic acidosis was different. With the Haemaccel-Ringer's prime, the metabolic acidosis was hyperchloremic (Delta Cl-, +9.50 mEq/l; confidence interval, 7.00-11.50). With Plasmalyte 148, the acidosis was induced by an increase in unmeasured anions, most probably acetate and gluconate. The resolution of these two processes was different because the excretion of chloride was slower than that of the unmeasured anions (Delta base excess from t1 to t3 = -1.60 for Haemaccel-Ringer's vs. +1.15 for Plasmalyte 148; P = 0.0062).

Conclusions

Cardiopulmonary bypass-induced metabolic acidosis appears to be iatrogenic in nature and derived from the effect of pump prime fluid on acid-base balance. The extent of such acidosis and its duration varies according to the type of pump prime.
Acid–Base Changes Caused by 5% Albumin versus 6% Hydroxyethyl Starch Solution in Patients Undergoing Acute Normovolemic Hemodilution
Authors: Rehm Markus , Orth Victoria , Scheingraber Stefan , Kreimeier Uwe , Brechtelsbauer Heinz , Finsterer Udilo
Published: November 2003

Background

Preoperative acute normovolemic hemodilution (ANH) is an excellent model for evaluating the effects of different colloid solutions that are free of bicarbonate but have large chloride concentrations on acid-base equilibrium.

Methods

In 20 patients undergoing gynecologic surgery, ANH to a hematocrit of 22% was performed. Two groups of 10 patients each were randomly assigned to receive either 5% albumin or 6% hydroxyethyl starch solutions containing chloride concentrations of 150 and 154 mm, respectively, during ANH. Blood volume (double label measurement of plasma and red cell volumes), pH, Paco2, and serum concentrations of sodium, potassium, chloride, lactate, ionized calcium, phosphate, albumin, and total protein were measured before and 20 min after completion of ANH. Strong ion difference was calculated as serum sodium plus serum potassium minus serum chloride minus serum lactate. The amount of weak plasma acid was calculated using a computer program.

Results

After ANH, blood volume was well maintained in both groups. ANH caused slight metabolic acidosis with hyperchloremia and a concomitant decrease in strong ion difference. Plasma albumin concentration decreased after hemodilution with 6% hydroxyethyl starch solution and increased after hemodilution with 5% albumin solution. Despite a three-times larger decrease in strong ion difference after ANH with 6% hydroxyethyl starch solution, the decrease in pH was nearly the same in both groups.

Conclusions

ANH with 5% albumin or 6% hydroxyethyl starch solutions led to metabolic acidosis. A dilution of extracellular bicarbonate or changes in strong ion difference and albumin concentration offer explanations for this type of acidosis.
Neuromuscular Monitoring at the Orbicularis Oculi May Overestimate the Blockade in Myasthenic Patients
Authors: Itoh Hironori , Shibata Keizo , Yoshida Masahiro , Yamamoto Ken
Published: November 2003

Background

In most publications about myasthenia, monitoring neuromuscular blockade during anesthesia is recommended. In healthy patients, the relation of blockade between muscles has been established, but there is little information about the relation in myasthenic patients. Our objective was to investigate whether the relation between the orbicularis oculi and adductor pollicis muscles is the same in healthy patients and myasthenic patients.

Methods

After anesthesia was induced with 4-6 mg/kg thiopental and 2 microg/kg fentanyl, followed by 2% sevoflurane and 60% nitrous oxide in oxygen, 10 healthy patients and 10 myasthenic patients received 0. 025 and 0.01 mg/kg vecuronium, respectively. Neuromuscular monitoring was performed with use of accelerometry at the orbicularis oculi and the adductor pollicis muscles by stimulating the temporal branch of the facial nerve and the ulnar nerve.

Results

The relation of blockade between these two muscles was not the same in healthy patients and myasthenic patients: in healthy patients, the maximum neuromuscular blockade with 0.025 mg/kg vecuronium was less in the orbicularis oculi than in the adductor pollicis (median 72% vs. 91%; P < 0.05); in contrast, in myasthenic patients, the blockade with 0.01 mg/kg vecuronium was greater in the orbicularis oculi than in the adductor pollicis (median 96% vs. 62%; P < 0.05).

Conclusion

Neuromuscular monitoring at the orbicularis oculi may overestimate blockade in myasthenic patients. Extubation must be performed when the muscle most sensitive to neuromuscular blocking agents is recovered. Therefore, neuromuscular monitoring at the orbicularis oculi is recommended to avoid persistent neuromuscular blockade in patients with myasthenia gravis.
Graded Hypercapnia and Cerebral Autoregulation during Sevoflurane or Propofol Anesthesia
Authors: McCulloch Timothy J. , Visco Elizabeth , Lam Arthur M.
Published: November 2003

Background

Hypercapnia abolishes cerebral autoregulation, but little is known about the interaction between hypercapnia and autoregulation during general anesthesia. With normocapnia, sevoflurane (up to 1.5 minimum alveolar concentration) and propofol do not impair cerebral autoregulation. This study aimed to document the level of hypercapnia required to impair cerebral autoregulation during propofol or sevoflurane anesthesia.

Methods

Eight healthy subjects received a remifentanil infusion and were anesthetized with propofol (140 microg. kg-1. min-1) and sevoflurane (1.0-1.1% end tidal) in a randomized crossover study. Ventilation was adjusted to achieve incremental increases in arterial carbon dioxide partial pressure (Paco2) until autoregulation was impaired. Cerebral autoregulation was tested by increasing the mean arterial pressure (MAP) from 80 to 100 mmHg with phenylephrine while measuring middle cerebral artery flow velocity by transcranial Doppler. The autoregulation index, which has a value ranging from 0 to 1, representing absent to perfect autoregulation, was calculated, and an autoregulation index of 0.4 or less represented significantly impaired autoregulation.

Results

The threshold Paco2 to significantly impair cerebral autoregulation ranged from 50 to 66 mmHg. The threshold averaged 56 +/- 4 mmHg (mean +/- SD) during sevoflurane anesthesia and 61 +/- 4 mmHg during propofol anesthesia (P = 0.03). Carbon dioxide reactivity measured at a MAP of 100 mmHg was 30% greater than that at a MAP of 80 mmHg.

Conclusions

Even mild hypercapnia can significantly impair cerebral autoregulation during general anesthesia. There is a significant difference between propofol anesthesia and sevoflurane anesthesia with respect to the effect of hypercapnia on cerebral autoregulation. This difference occurs at clinically relevant levels of Paco2. When inducing hypercapnia, carbon dioxide reactivity is significantly affected by the MAP.
Plasma and Urinary Cytokine Homeostasis and Renal Dysfunction during Cardiac Surgery
Authors: Gormley Sheena M. C. , McBride William T. , Armstrong Marilyn A. , Young Ian S. , McClean Elizabeth , MacGowan Simon W. , Campalani Gianfranco , McMurray Terence J.
Published: November 2003

Background

Cardiac surgery induces changes in plasma cytokines. Proinflammatory cytokines have been associated with a number of renal diseases. The proinflammatory cytokines interleukin 8 (IL-8), tumor necrosis factor alpha (TNFalpha), and interleukin 1beta (IL-1beta) are smaller than the antiinflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra), and TNF soluble receptor 2 (TNFsr2), and thus undergo glomerular filtration more readily. Accordingly, this study investigated the relation between plasma and urinary cytokines and proximal renal dysfunction during cardiac surgery.

Methods

Twenty patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were studied. Blood and urine samples were analyzed for proinflammatory and antiinflammatory cytokines. Proximal tubular dysfunction was measured using urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha1-microglobulin/creatinine ratios.

Results

Plasma IL-8, IL-10, IL-1ra, and TNFsr2 values were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated. Urinary NAG/creatinine and alpha1-microglobulin/creatinine ratios were also elevated. Plasma TNFalpha at 2 h correlated with urinary NAG/creatinine ratio at 2 and 6 h (P < 0.05) and with urinary IL-1ra at 2 h (P < 0.05). Plasma IL-8 at 2 h correlated with NAG/creatinine at 6 h (P < 0.05). Urinary IL-1ra correlated with urinary NAG/creatinine ratio after cross-clamp release and 2 and 6 h after CPB (P < 0.05).

Conclusions

Cardiac surgery using CPB leads to changes in plasma and urinary cytokine homeostasis that correlate with renal proximal tubular dysfunction. This dysfunction may be related to the renal filtration of proinflammatory mediators. Renal autoprotective mechanisms may involve the intrarenal generation of antiinflammatory cytokines.
Comparison of the Costs and Recovery Profiles of Three Anesthetic Techniques for Ambulatory Anorectal Surgery
Authors: Li Shitong , Coloma Margarita , White Paul F. , Watcha Mehernoor F. , Chiu Jen Wun , Li Hong , Huber Philip J.
Published: November 2003

Background

Given the current practice environment, it is important to determine the anesthetic technique with the highest patient acceptance and lowest associated costs. The authors compared three commonly used anesthetic techniques for anorectal procedures in the ambulatory setting.

Methods

Ninety-three consenting adult outpatients undergoing anorectal surgery were randomly assigned to one of three anesthetic treatment groups: group 1 received local infiltration with a 30-ml mixture containing 15 ml lidocaine, 2%, and 15 ml bupivacaine, 0.5%, with epinephrine (1:200,000) in combination with intravenous sedation using a propofol infusion, 25-100 microg. kg-1. min-1; group 2 received a spinal subarachnoid block with a combination of 30 mg lidocaine and 20 microg fentanyl with midazolam, 1-2-mg intravenous bolus doses; and group 3 received general anesthesia with 2.5 mg/kg propofol administered intravenously and 0.5-2% sevoflurane in combination with 65% nitrous oxide. In groups 2 and 3, the surgeon also administered 10 ml of the previously described local anesthetic mixture at the surgical site before the skin incision.

Results

The mean costs were significantly decreased in group 1 ($69 +/- 20 compared with $104 +/- 18 and $145 +/- 25 in groups 2 and 3, respectively) because both intraoperative and recovery costs were lowest (P < 0.05). Although the surgical time did not differ among the three groups, the anesthesia time and times to oral intake and home-readiness were significantly shorter in group 1 (vs. groups 2 and 3). There was no significant difference among the three groups with respect to the postoperative side effects or unanticipated hospitalizations. However, the need for pain medication was less in groups 1 and 2 (19% and 19% vs. 45% for group 3; P < 0.05). Patients in group 1 had no complaints of nausea (vs. 3% and 26% in groups 2 and 3, respectively). More patients in group 1 (68%) were highly satisfied with the care they received than in groups 2 (58%) and 3 (39%).

Conclusions

The use of local anesthesia with sedation is the most cost-effective technique for anorectal surgery in the ambulatory setting.
Effect of Patient-triggered Ventilation on Respiratory Workload in Infants after Cardiac Surgery
Authors: Takeuchi Muneyuki , Imanaka Hideaki , Miyano Hiroshi , Kumon Keiji , Nishimura Masaji
Published: November 2003

Background

Patient-triggered ventilation (PTV) is commonly used in adults to avoid dyssynchrony between patient and ventilator. However, few investigations have examined the effects of PTV in infants. Our objective was to determine if pressure-control PTV reduces infants' respiratory workloads in proportion to the level of pressure control. We also explored which level of pressure control provided respiratory workloads similar to those after the extubation of the trachea.

Methods

When seven post-cardiac surgery infants, aged 1 to 11 months, were to be weaned with the pressure-control PTV, we randomly applied five levels of pressure control: 0, 4, 8, 12, and 16 cm H2O. All patients were ventilated with assist-control mode, triggering sensitivity of 1 l/min, and positive end-expiratory pressure of 3 cm H2O. After establishing steady state conditions at each level of pressure control, arterial blood gases were analyzed and esophageal pressure (Pes), airway pressure, and airflow were measured. Inspiratory work of breathing (WOB) was calculated using a Campbell diagram. A modified pressure-time product (PTPmod) and the negative deflection of Pes were calculated from the Pes tracing below the baseline. The measurement was repeated after extubation.

Results

Pressure-control PTV supported every spontaneous breath. By decreasing the level of pressure control, respiratory rate increased, tidal volume decreased, and as a result, minute ventilation and arterial carbon dioxide partial pressure were maintained stable. The WOB, PTPmod, and negative deflection of Pes increased as pressure control level was decreased. The WOB and PTPmod at 4 cm H2O pressure control and 0 cm H2O pressure control and after extubation were significantly greater than those at the pressure control of 16, 12, and 8 cm H2O (P < 0.05). The WOB and PTPmod were almost equivalent after extubation and at 4 cm H2O pressure control.

Conclusions

Work of breathing and PTPmod were changed according to the pressure control level in post-cardiac surgery infants. PTV may be feasible in infants as well as in adults.
Sex Differences in Morphine Analgesia
Authors: Sarton Elise , Olofsen Erik , Romberg Raymonda , den Hartigh Jan , Kest Benjamin , Nieuwenhuijs Diederik , Burm Anton , Teppema Luc , Dahan Albert
Published: November 2003

Background

Animal and human studies indicate the existence of important sex-related differences in opioid-mediated behavior. In this study the authors examined the influence of morphine on experimentally induced pain in healthy male and female volunteers.

Methods

Young healthy men and women (10 of each sex) received intravenous morphine (bolus 0.1-mg/kg dose followed by an infusion of 0.030 mg. kg-1. h-1 for 1 h). Pain threshold and pain tolerance in response to a gradual increase in transcutaneous electrical stimulation, as well as plasma concentrations of morphine and its major metabolites (morphine-6-glucuronide and morphine-3-glucuronide) were determined at regular intervals up to 7 h after the start of morphine infusion. A population pharmacodynamic model was used to analyze the morphine-induced changes in stimulus intensity. The improvement of the model fits by inclusion of covariates (sex, age, weight, lean body mass) was tested for significance. The model is characterized by baseline current, a rate constant for equilibrium between plasma and effect-site morphine concentrations (ke0), and analgesic potency (AC50, or the morphine concentration causing a 100% increase in stimulus intensity for response).

Results

The inclusion of the covariates age, weight, and lean body mass did not improve the model fits for any of the model parameters. For both pain threshold and tolerance, a significant dependency on sex was observed for the parameters ke0 (pain threshold: 0.0070 +/- 0.0013 (+/- SE) min-1 in men vs. 0.0030 +/- 0. 0005 min-1 in women; pain tolerance: 0.0073 +/- 0.0012 min-1 in men vs. 0.0024 +/- 0.0005 min-1 in women) and AC50 (pain threshold: 71.2 +/- 10.5 nm in men vs. 41.7 +/- 8.4 nm in women; pain tolerance: 76. 5 +/- 7.4 nm in men vs. 32.9 +/- 7.9 nm in women). Baseline currents were similar for both sexes: 21.4 +/- 1.6 mA for pain threshold and 39.1 +/- 2.3 mA for pain tolerance. Concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide did not differ between men and women.

Conclusions

These data show sex differences in morphine analgesia, with greater morphine potency but slower speed of onset and offset in women. The data are in agreement with observations of sex differences in morphine-induced respiratory depression and may explain higher postoperative opioid consumption in men relative to women.
Neuroprotective Effects of Riluzole and Ketamine during Transient Spinal Cord Ischemia in the Rabbit
Authors: Lips Jeroen , de Haan Peter , Bodewits Pieter , Vanicky Ivo , Dzoljic Misa , Jacobs Michael J. , Kalkman Cor J.
Published: November 2003

Background

Massive release of central excitatory neurotransmitters is an important initial step in ischemic neuronal injury, and modification of this process may provide neuroprotection. We studied the protective effects of the voltage-dependent sodium channel antagonist riluzole and the N-methyl-d-aspartate receptor antagonist ketamine on hind limb motor function and histopathologic outcome in an experimental model of spinal cord ischemia.

Methods

Temporary spinal cord ischemia was induced by 29 min of infrarenal balloon occlusion of the aorta in 60 anesthetized New Zealand white rabbits. Animals were randomly assigned to one of four treatment groups (n = 15 each): group C, saline (control); group R, riluzole, 8 mg/kg intravenously; group K, ketamine, 55 mg/kg intravenously; group RK, riluzole and ketamine. After reperfusion, riluzole treatment was continued with intraperitoneal infusions. Normothermia (38 degrees C) was maintained during ischemia, and rectal temperature was assessed before and after intraperitoneal infusions. Neurologic function, according to Tarlov's criteria, was evaluated every 24 h, and infarction volume and the number of eosinophilic neurons and viable motoneurons in the lumbosacral spinal cord was evaluated after 72 h.

Results

Neurologic outcome was better in groups R and RK than in groups C and K. All animals in group C (100%) and all animals but one in group K (93%) were paraplegic 72 h after the ischemic insult versus 53% in group R and 67% in group RK (P < 0.01 each). More viable motoneurons were present in groups R and RK than in controls (P < 0.05).

Conclusions

The data indicate that treatment with riluzole can increase the tolerance of spinal cord motoneurons to a period of normothermic ischemia. Intraischemic ketamine did not provide neuroprotection in this model.
Altered Expression of Cardiac Myosin Isozymes Associated with the Malignant Hyperthermia Genotype in Swine
Authors: Liou Ying-Ming , Jiang Meei Jyh , Wu Ming-Che
Published: November 2003

Background

Anesthetic-induced malignant hyperthermia (MH) in humans and pigs is associated with dramatic alterations in cardiac function. However, it remains controversial as to whether MH-associated cardiac symptoms represent a primary difference of myocardium or a secondary alteration consequent to increases in the hyperthermic stress. Here the authors describe changes in myosin isoform expression in the hearts of MH-susceptible pigs with and without prior exposure to halothane.

Methods

One group of pigs was diagnosed as MH susceptible by halothane challenge and Hal-1843 nucleotide examination. To determine if there is an effect of halothane exposure, another group of pigs was diagnosed by simple MH genotyping without exposure to halothane. After diagnosis and genotyping, animals with and without exposure to halothane were killed to study cardiac myosin isozyme distributions, cardiac myofibrillar adenosine triphosphatase (ATPase) activity, and the steepness of the Ca2+-ATPase activity relation in the hearts of normal and susceptible pigs. The altered myosin isozyme expression was analyzed by pyrophosphate gel electrophoresis.

Results

Malignant hyperthermia-susceptible animals with the prior halothane challenge showed an increased V1 myosin (-44%) expression, increased myofibrillar ATPase activity (-25%) and increased steepness of the Ca2+-ATPase activity relation. Without exposure to halothane, no change of myofibrillar ATPase activity was found in the hearts of different genotyped pigs, but there was a small increase in expression of V1 myosin (-5%) in the mutant (TT).

Conclusions

The potential modulation of V1 myosin expression occurs in the hearts of MH-susceptible pigs. The added stress by halothane challenge would further cause a V3 --> V1 shift, which may be attributed to the long-term effects of hyperthermic stress.
Accuracy and Reliability of the Self-inflating Bulb to Verify Tracheal Intubation in Out-of-hospital Cardiac Arrest Patients
Authors: Tanigawa Koichi , Takeda Taku , Goto Eiichi , Tanaka Keiichi
Published: November 2003

Background

To determine the sensitivity and specificity of the self-inflating bulb (SIB) to verify tracheal intubation in out-of-hospital cardiac arrest patients.

Methods

Sixty-five consecutive adult patients with out-of-hospital cardiac arrest were enrolled. Patients were provided chest compression and ventilation by either ba-valve-mask or the esophageal tracheal double-lumen airway by ambulance crews when they arrived at the authors' department. Immediately after intubation in the emergency department, the endotracheal tube position was tested by the SIB and end-tidal carbon dioxide (ETCO2) monitor using an infrared carbon dioxide analyzer. We observed the SIB reinflating for 10 s, and full reinflation within 4 s was defined as a positive result (tracheal intubation).

Results

Five esophageal intubations occurred, and the SIB correctly identified all esophageal intubations. Of the 65 tracheal intubations, the SIB correctly identified 47 tubes placed in the trachea (72.3%). Delayed but full reinflation occurred in one tracheal intubation during the 10-s observation period. Fifteen tracheal intubations had incomplete reinflation during the observation period, and two tracheal intubations did not achieve any reinflation. Thirty-nine tracheal intubations were identified by ETCO2 (60%). When the SIB test is combined with the ETCO2 detection, 59 tracheal intubations were identified with a 90.8% sensitivity.

Conclusions

The authors found a high incidence of false-negative results of the SIB in out-of-hospital cardiac arrest patients. Because no single test for verifying endotracheal tube position is reliable, all available modalities should be tested and used in conjunction with proper clinical judgment to verify tracheal intubation in cases of out-of-hospital cardiac arrest.
Influence of Hypovolemia on the Pharmacokinetics and the Electroencephalographic Effect of Propofol in the Rat
Authors: De Paepe Peter , Belpaire Frans M. , Rosseel Marie T. , Van Hoey Gert , Boon Paul A. , Buylaert Walter A.
Published: November 2003

Background

Hypovolemia decreases the dose requirement for anesthetics, but no data are available for propofol. As it is impossible to study this in patients, a rat model was used in which the influence of hypovolemia on the pharmacokinetics and pharmacodynamics of propofol was investigated.

Methods

Animals were randomly allocated to either a control (n = 9) or a hypovolemia (n = 9) group, and propofol was infused (150 mg x kg(-1) x h(-1)) until isoelectric periods of 5 s or longer were observed in the electroencephalogram. The changes observed in the electroencephalogram were quantified using aperiodic analysis and used as a surrogate measure of hypnosis. The righting reflex served as a clinical measure of hypnosis.

Results

The propofol dose needed to reach the electroencephalographic end point in the hypovolemic rats was reduced by 60% (P < 0.01). This could be attributed to a decrease in propofol clearance and in distribution volume. Protein binding was similar in both groups. To investigate changes in end organ sensitivity during hypovolemia, the electroencephalographic effect versus effect-site concentration relation was studied. The effect-blood concentration relation was biphasic, exhibiting profound hysteresis in both hypovolemic and control animals. Semiparametric minimization of this hysteresis revealed similar equilibration half-lives in both groups. The biphasic effect-concentration relation was characterized by descriptors showing an increased potency of propofol during hemorrhage. The effect-site concentration at the return of righting reflex was 23% (P < 0.01) lower in the hypovolemic animals, also suggesting an increased end organ sensitivity.

Conclusions

An increased hypnotic effect of propofol occurs during hypovolemia in the rat and can be attributed to changes in both pharmacokinetics and end organ sensitivity.
Measurement of Individual Clinical Productivity in an Academic Anesthesiology Department
Authors: Abouleish Amr E. , Zornow Mark H. , Levy Ronald S. , Abate James , Prough Donald S.
Published: November 2003

Background

The ability to measure productivity, work performed, or contributions toward the clinical mission has become an important issue facing anesthesiology departments in private practice and academic settings. Unfortunately, the practice and billing of anesthesia services makes it difficult to quantify individual productivity. This study examines the following methods of measuring individual productivity: normalized clinical days per year (nCD/yr); time units per operating-room day worked (TU/OR day); normalized time units per year (nTU/yr); total American Society of Anesthesiologists (ASA) units per OR day (tASA/OR day); and normalized total ASA units per year (ntASA/yr).

Methods

Billing and scheduling data for clinical activities of faculty members of an anesthesiology department at a university medical center were collected and analyzed for the 1998 fiscal year. All clinical sites and all clinical faculty anesthesiologists were included unless they spent less than 20% of their time during the fiscal year providing clinical care, i.e., less than 0.2 clinical full-time equivalent. Outliers, defined as faculty who had productivity greater or less than 1 SD from the mean, were examined in detail.

Results

Mean and median values were reported for each measurement, and different groups of outliers were identified. nCD/yr identified faculty who worked more than their clinical full-time equivalent would have predicted. TU/OR day and tASA/OR day identified apparently low-productivity faculty as those who worked a large portion of their time in obstetric anesthesia or an ambulatory surgicenter. tASA/OR day identified specialty anesthesiologists as apparently high-productivity faculty. nTU/yr and ntASA/yr were products of the per-OR day measurement and nCD/yr.

Conclusion

Each of the measurements studied values certain types of productivity more than others. By defining what type of service is most important to reward, the most appropriate measure or combination of measures of productivity can be chosen. In the authors' department, nCD/yr is the most useful measure of individual productivity because it measures an individual anesthesiologist's contribution to daily staffing, includes all clinical sites, is independent of nonanesthesia factors, and is easy to collect and determine.
Peribulbar versus Retrobulbar Anesthesia for Ophthalmic Surgery
Authors: Ripart Jacques , Lefrant Jean-Yves , de La Coussaye Jean-Emmanuel , Prat-Pradal Dominique , Vivien Bruno , Eledjam Jean-Jacques
Published: November 2003

Background

Peribulbar and retrobulbar anesthesia have long been opposed on the basis of the existence of an intermuscular membrane, which is supposed to separate the intraconal from the extraconal spaces in a water-tight fashion. A local anesthetic injected outside the cone should spread through this septum to reach the nerves to be blocked. The existence of this septum is questioned. The aim of this study was to compare the spread of a colored latex dye injected intraconally or extraconally to simulate both retrobulbar and peribulbar anesthesia.

Methods

The authors used 10 heads from human cadavers. For each head, one eye was injected intraconally, and the other eye was injected extraconally. The heads were then frozen and sectioned into thin slices following various planes. They were then photographed and observed.

Results

There was no evidence of the existence of an intermuscular septum separating the intraconal and extraconal spaces. Those two spaces appeared to be part of a common spreading space, the corpus adiposum of the orbit.

Conclusions

These results are in accord with the fact that clinical studies were not able to clearly demonstrate that retrobulbar anesthesia is more efficient than peribulbar anesthesia. On the basis of a similar clinical efficacy of the two techniques as a result of similar spreading of the local anesthetic injected, and a potentially higher risk of introducing the needle into the muscular cone, the authors recommend replacing retrobulbar anesthesia with peribulbar anesthesia.
Cytochrome P-450 2B6 Is Responsible for Interindividual Variability of Propofol Hydroxylation by Human Liver Microsomes
Authors: Court Michael H. , Duan Su X. , Hesse Leah M. , Venkatakrishnan Karthik , Greenblatt David J.
Published: November 2003

Background

Oxidation of propofol to 4-hydroxypropofol represents a significant pathway in the metabolism of this anesthetic agent in humans. The aim of this study was to identify the principal cytochrome P-450 (CYP) isoforms mediating this biotransformation.

Methods

Propofol hydroxylation activities and enzyme kinetics were determined using human liver microsomes and cDNA-expressed CYPs. CYP-specific marker activities and CYP2B6 protein content were also quantified in hepatic microsomes for correlational analyses. Finally, inhibitory antibodies were used to ascertain the relative contribution of CYPs to propofol hydroxylation by hepatic microsomes.

Results

Propofol hydroxylation by hepatic microsomes showed more than 19-fold variability and was most closely correlated to CYP2B6 protein content (r = 0.904), and the CYP2B6 marker activities, S-mephenytoin N-demethylation (r = 0.919) and bupropion hydroxylation (r = 0.854). High- and intermediate-activity livers demonstrated high-affinity enzyme kinetics (K(m) < 8 microm), whereas low-activity livers displayed low-affinity kinetics (K(m) > 80 microm). All of the CYPs evaluated were capable of hydroxylating propofol; however, CYP2B6 and CYP2C9 were most active. Kinetic analysis indicated that CYP2B6 is a high-affinity (K(m) = 10 +/- 2 microm; mean +/- SE of the estimate), high-capacity enzyme, whereas CYP2C9 is a low-affinity (K(m) = 41 +/- 8 microm), high-capacity enzyme. Furthermore, immunoinhibition showed a greater contribution of CYP2B6 (56 +/- 22% inhibition; mean +/- SD) compared with CYP2C isoforms (16 +/- 7% inhibition) to hepatic microsomal activity.

Conclusions

Cytochrome P-450 2B6, and to a lesser extent CYP2C9, contribute to the oxidative metabolism of propofol. However, CYP2B6 is the principal determinant of interindividual variability in the hydroxylation of this drug by human liver microsomes.
Leukocytes Can Enhance Platelet-mediated Aggregation and Thromboxane Release via Interaction of P-selectin Glycoprotein Ligand 1 with P-selectin
Authors: Faraday Nauder , Scharpf Robert B. , Dodd-o Jeffrey M. , Martinez Elizabeth A. , Rosenfeld Brian A. , Dorman Todd
Published: November 2003

Background

Platelet--leukocyte conjugates have been observed in patients with unstable coronary syndromes and after cardiopulmonary bypass. In vitro, the binding of platelet P-selectin to leukocyte P-selectin glycoprotein ligand-1 (PSGL1) mediates conjugate formation; however, the hemostatic implications of these cell--cell interactions are unknown. The aims of this study were to determine the ability of leukocytes to modulate platelet agonist--induced aggregation and secretion in the blood milieu, and to investigate the role of P-selectin and PSGL-1 in mediating these responses.

Methods

Blood was drawn from healthy volunteers for in vitro analysis of platelet agonist--induced aggregation, secretion (adenosine triphosphate, beta-thromboglobulin, and thromboxane), and platelet-leukocyte conjugate formation. Experiments were performed on live cells in whole blood or plasma to simulate physiologic conditions. Whole-blood impedance and optical aggregometry, flow cytometry, and enzyme-linked immunosorbent assays were performed in the presence and absence of blocking antibodies to P-selectin and PSGL1. The platelet-specific agonists, thrombin receptor activating peptide and adenosine diphosphate, were used to elicit platelet activation responses.

Results

Inhibition of platelet--leukocyte adherence by P- selectin and PSGL1 antibodies decreased agonist--induced aggregation in whole blood. The presence of leukocytes in platelet-rich plasma increased aggregation, and this increase was attenuated by P-selectin blocking antibodies. Data from flow cytometry confirmed that platelet-leukocyte conjugate formation contributed to aggregation responses. Blocking antibodies reduced platelet agonist--induced thromboxane release but had no impact on adenosine triphosphate and beta-thomboglobulin secretion.

Conclusions

Leukocytes can enhance platelet agonist--induced aggregation and thromboxane release in whole blood and platelet-rich plasma under shear conditions in vitro. Interaction of platelet P-selectin with leukocyte PSGL1 contributes substantially to these effects.
The Cardiac Anesthesia Risk Evaluation Score
Authors: Dupuis Jean-Yves , Wang Feng , Nathan Howard , Lam Miu , Grimes Scott , Bourke Michael
Published: November 2003

Background

The Cardiac Anesthesia Risk Evaluation (CARE) score is a simple risk classification for cardiac surgical patients. It is based on clinical judgment and three clinical variables: comorbid conditions categorized as controlled or uncontrolled, surgical complexity, and urgency of the procedure. This study compared the CARE score with the Parsonnet, Tuman, and Tu multifactorial risk indexes for prediction of mortality and morbidity after cardiac surgery.

Methods

In this prospective study, 3,548 cardiac surgical patients from one institution were risk stratified by two investigators using the CARE score and the three tested multifactorial risk indexes. All patients were also given a CARE score by their attending cardiac anesthesiologist. The first 2,000 patients served as a reference group to determine discrimination of each classification with receiver operating characteristic curves. The following 1,548 patients were used to evaluate calibration using the Pearson chi-square goodness-of-fit test.

Results

The areas under the receiver operating characteristic curves for mortality and morbidity were 0.801 and 0.721, respectively, with the CARE score rating by the investigators; 0.786 and 0.710, respectively, with the CARE score rating by the attending anesthesiologists (n = 8); 0.808 and 0.726, respectively, with the Parsonnet index; 0.782 and 0.697, respectively, with the Tuman index; 0.770 and 0.724 with the Tu index, respectively. All risk models had acceptable calibration in predicting mortality and morbidity, except for the Parsonnet classification, which failed calibration for morbidity (P = 0.026).

Conclusions

The CARE score performs as well as multifactorial risk indexes for outcome prediction in cardiac surgery. Cardiac anesthesiologists can integrate this score in their practice and predict patient outcome with acceptable accuracy.
Cardiovascular Effects of Sevoflurane, Isoflurane, Halothane, and Fentanyl–Midazolam in Children with Congenital Heart Disease
Authors: Rivenes Shannon M. , Lewin Mark B. , Stayer Stephen A. , Bent Sabrina T. , Schoenig Heather M. , McKenzie E. Dean , Fraser Charles D. , Andropoulos Dean B.
Published: November 2003

Background

The cardiovascular effects of halogenated anesthetic agents in children with normal hearts have been studied, but data in children with cardiac disease are limited. This study compared the effects of halothane, isoflurane, sevoflurane, and fentanyl-midazolam on systemic and pulmonary hemodynamics and myocardial contractility in patients with congenital heart disease.

Methods

Fifty-four patients younger than age 14 scheduled to undergo congenital heart surgery were randomized to receive halothane, sevoflurane, isoflurane, or fentanyl-midazolam. Cardiovascular and echocardiographic data were recorded at baseline and at randomly ordered 1 and 1.5 minimum alveolar concentrations, or predicted equivalent fentanyl-midazolam plasma concentrations. The shortening fraction and ejection fraction (using the modified Simpson rule) were calculated. Cardiac index was assessed by the velocity-time integral method.

Results

Halothane caused a significant decrease in mean arterial pressure, ejection fraction, and cardiac index, preserving only heart rate at baseline levels. Fentanyl-midazolam in combination caused a significant decrease in cardiac index secondary to a decrease in heart rate; contractility was maintained. Sevoflurane maintained cardiac index and heart rate and had less profound hypotensive and negative inotropic effects than halothane. Isoflurane preserved both cardiac index and ejection fraction, had less suppression of mean arterial pressure than halothane, and increased heart rate.

Conclusions

Isoflurane and sevoflurane preserved cardiac index, and isoflurane and fentanyl-midazolam preserved myocardial contractility at baseline levels in this group of patients with congenital heart disease. Halothane depressed cardiac index and myocardial contractility.