bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Intrathecally Administered Lamotrigine, a Glutamate Release Inhibitor, on Short- and Long-term Models of Hyperalgesia in Rats
Authors: Klamt Jyrson G.
Published: November 2003

Background

Lamotrigine is a sodium channel blocker that inhibits the neuronal release of glutamate. Systemic administration of lamotrigine induces analgesia in short- and long-term models of hyperalgesia in rats. Considering the key role of N-methyl-D-aspartate receptors in the sensitization of dorsal horn neurons that leads to hyperalgesia, the author hypothesizes that intrathecally injected lamotrigine would be effective in reducing the hyperalgesia.

Methods

Short-term hyperalgesia was induced by unilateral intraplantar injection of prostaglandin E2. Long-term hyperalgesia was produced by treating rats with streptozotocin, which causes diabetic neuropathy and, in a different group of animals, by loose ligation of the sciatic nerve (chronic constriction injury). Hyperalgesia was assessed by measuring withdrawal reaction time after paw pressure, and analgesia was measured by the thermal tail-flick test.

Results

In the short-term model, intrathecally administered lamotrigine (12.5, 25.0, and 100.0 microg) produced a dose-dependent increase in the reaction time of the hyperalgesic paw. The highest dose that completely restored the reaction time to control levels (26-29 s) from the hyperalgesic levels (12-15 s) did not affect the reaction time of the normal contralateral paw. In the tail-flick test, a consistent effect could be observed only with doses of 200 microg, which caused transient motor impairment of the hind paws. In the long-term models of hyperalgesia, intrathecally administered lamotrigine produced a dose-dependent and long-lasting (24-48 h) antihyperalgesic effect.

Conclusions

Intrathecally administered lamotrigine produced a spinal, dose-dependent, and long-lasting antihyperalgesic effect in short- and long-term neuropathic models of hyperalgesia.
The Sensitivity and Specificity of the Caffeine-Halothane Contracture Test
Authors: Allen Gregory C. , Larach Marilyn Green , Kunselman Allen R.
Published: November 2003

Background

The caffeine-halothane contracture test (CHCT) is the only recognized laboratory test to diagnose malignant hyperthermia (MH). The authors report the results of their analysis of pooled data from the North American Malignant Hyperthermia Registry database to determine the sensitivity and specificity of the CHCT.

Methods

The MH Clinical Grading Scale was used to identify 32 case subjects who were "almost certain" to be MH susceptible based on clinical criteria alone. Their CHCT results were compared with those of a group of 120 control subjects considered to be at low risk for MH. Diagnostic thresholds of the CHCT were adjusted, and its component tests were combined to generate receiver operating characteristic curves. The maximal Youden index for each component test was chosen as the diagnostic threshold indicative of MH susceptibility.

Results

The highest sensitivity (97%; 95% CI, 84-100%) was achieved with a two-component test with thresholds of > or = 0.5 g contracture for 3% halothane, > or = 0.3 g contracture at 2 mM caffeine, or both, considered positive for MH. The test specificity was 78% (95% CI, 69-85%). The addition of other CHCT component tests did not improve CHCT sensitivity or specificity.

Conclusion

The CHCT achieves high sensitivity and acceptable specificity as a clinical laboratory diagnostic test when it is performed according to published standards. However, it cannot be used as a screening test because of the low prevalence of MH in the general population.
The Response to Repeated Nitric Oxide Inhalation Is Inconsistent in Patients with Acute Respiratory Distress Syndrome
Authors: Treggiari-Venzi Miriam , Ricou Bara , Romand Jacques-Andre , Suter Peter M.
Published: November 2003

Background

Nitric oxide (NO) is administered frequently in patients with acute respiratory distress syndrome (ARDS) and pulmonary hypertension. The efficacy of this therapy over several days is not well known. The authors first determined the consistency of the response to repeated administration of NO and then the baseline variables that were associated with improvement in patients with severe ARDS.

Methods

In a prospective trial, 32 mechanically ventilated patients with severe ARDS received 10 parts per million NO by inhalation. In 22 of these patients, its effect was tested repeatedly (up to four times) in several days. Improvement was defined as an increase >10% in the ratio of pressure of oxygen in arterial blood (P(aO2)) to the inspiratory pressure of oxygen (FIO2) from baseline. Patients showing such an improvement were maintained on NO inhalation.

Results

Twelve of the 22 patients (54%) showed a clinically significant and reproducible increase in the P(aO2)/FIO2 ratio with NO, from 74 +/- 30 mmHg (mean +/- SD) to 95 +/- 41 mmHg (P < 0.001). In three patients (14%), P(aO2) did not improve, even with multiple exposures. In seven patients (32%), an inconsistent response was seen on different days. Mean pulmonary artery pressure decreased for the entire group from 34 +/- 10 mmHg to 29 +/- 9 mmHg (P < 0.01), but this decrease did not correlate with the increase in P(aO2) in individual patients. The baseline P(aO2)/FIO2 ratio and mixed venous oxygenation (P(vO2)) were significantly lower, and the venous admixture was greater in patients showing beneficial effects of NO inhalation on P(aO2).

Conclusions

Repeated NO inhalation caused a consistent improvement in P(aO2) in about one half of these patients with severe ARDS; no significant benefit or inconsistent effects on pulmonary gas exchange were noted in the others. These findings could be related to the complexity of the mechanisms regulating the vasomotor changes in this syndrome. Severe baseline hypoxemia may be associated with a more favorable effect of NO on P(aO2).
A Comparison of the Intubation Conditions between Mivacurium and Rocuronium during Balanced Anesthesia
Authors: Pino Richard M. , Ali Hassan H. , Denman William T. , Barrett Pamela S. , Schwartz Ann
Published: November 2003

Background

Comparisons of the intubation conditions with mivacurium and rocuronium from previous reports are confounded by the use of varied induction regimens. The authors compared intubation conditions of mivacurium, rocuronium, and a placebo at 90 s and their recovery profiles during anesthesia with nitrous oxide, oxygen, and propofol.

Methods

After induction with midazolam, fentanyl, and propofol in a randomized blinded study, 100 patients received one of the following treatments: 0.25 mg/kg mivacurium in divided doses (0.15 mg/kg followed by 0.1 mg/kg 30 s later); 0.45, 0.6, 0.9, or 1.2 mg/kg rocuronium; or placebo. Evoked thumb adduction was measured throughout. Intubation was attempted 90 s after the initial dose of mivacurium and other treatment doses by a "blinded" physician. Intubating conditions were graded as excellent, good, poor, or not possible. Spontaneous recovery was studied until a 25% initial twitch height was reached. Mean arterial blood pressure and heart rate changes between groups were determined before induction through 6 min after administration of the study drugs.

Results

There were no important changes or intergroup differences in mean arterial blood pressure and heart rate. Intubation conditions were good or excellent for both mivacurium and rocuronium at the 0.9 mg/kg dose (93%) and at the 1.2 mg/kg dose (100%). Rocuronium at the 0.6 mg/kg dose was excellent in 27% of patients, whereas rocuronium at the 0.45 mg/kg dose had the least number of excellent conditions and the most poor or not possible assessments. Patients given placebo could not be intubated. Times to maximum blockade for 0.9 and 1.2 mg/kg rocuronium were the shortest. The times to 25% recovery for 0.6 mg/kg rocuronium (mean +/- SD = 27 +/- 8.6 min), 0.9 mg/kg (43.1 +/- 10.8), and 1.2 mg/kg (62.3 +/- 17.4 min) were significantly longer than were those for mivacurium (17.4 +/- 6.2 min).

Conclusions

Mivacurium in a 0.25 mg/kg divided dose and rocuronium at 0.9 mg/kg and 1.2 mg/kg provide good or excellent intubation conditions at 90 s in most patients. Rocuronium was faster in onset at the higher doses (0.9 and 1.2 mg/kg) but had more prolonged recovery times to 25% single twitch height.
Recovery of Evoked Potential Amplitude after Cerebral Arterial Air Embolism in the Rabbit
Authors: Hindman Bradley J. , Dexter Franklin , Enomoto Sakae , Subieta Alberto , Smith Tom , Cutkomp Johann
Published: November 2003

Background

Cerebral arterial air embolism (CAAE) may cause neurologic injury during cardiac surgery. It is not known whether cardiopulmonary bypass (CPB) increases or decreases brain injury from CAAE compared with the normal circulation.

Methods

A model of CAAE was produced by injection of 50 microl/kg air into the internal carotid artery of methohexital-anesthetized New Zealand white rabbits. Somatosensory-evoked potential (SSEP) amplitude was measured serially as a marker of neurologic recovery. In experiment A, saline rather than air was injected to control for surgical manipulation and time in CPB (n = 4) and nonheparinized non-CPB (n = 4) animals. In experiment B, 50 microl/kg air was injected in CPB (n = 11) and nonheparinized non-CPB (n = 11) animals. In experiment C, non-CPB animals (n = 6) were given heparin according to the same protocol as for CPB.

Results

In experiment A, SSEP latencies and amplitudes did not differ between CPB and non-CPB conditions. In experiment B, there was no SSEP recovery 5 min after CAAE in either CPB or non-CPB animals. Thereafter, SSEP recovery was less in CPB animals than in non-CPB animals at 30 min (9 +/- 12% vs. 29 +/- 20%; P = 0.009) and 60 min (18 +/- 15% vs. 39 +/- 22%; P = 0.030) after CAAE. Ninety-minute SSEP recovery did not differ between CPB and non-CPB groups (at 24 +/- 19% vs. 39 +/- 24%, respectively; P = 0.146). In experiment C (heparinized non-CPB), SSEP recovery 5, 30, 60, and 90 min after CAAE was 67 +/- 48%, 72 +/- 47%, 80 +/- 35%, and 77 +/- 35%, respectively.

Conclusions

Somatosensory-evoked potential recovery after CAAE is no better (and is probably worse) during CPB than during normal circulation. The adverse effect of CPB occurs despite heparinization, which, under non-CPB conditions, appears to be protective. Therapies in addition to heparin are needed during CPB to reduce neurologic injury from CAAE.
Stereoselective Effects of Etomidate Optical Isomers on Gamma-aminobutyric Acid Type A Receptors and Animals
Authors: Tomlin Sarah L. , Jenkins Andrew , Lieb William R. , Franks Nicholas P.
Published: November 2003

Background

The intravenous anesthetic etomidate is optically active and exists in two mirror-image enantiomeric forms. However, although the R(+) isomer is used as a clinical anesthetic, quantitative information on the relative potencies of the R(+) and S(-) isomers is lacking. These data could be used to test the relevance of putative molecular targets.

Methods

The anesthetic concentrations for a half-maximal effect (EC50) needed to induce a loss of righting reflex in tadpoles (Rana temporaria) were determined for both etomidate enantiomers. The effects of the isomers on gamma-aminobutyric acid (GABA)-induced currents in stably transfected mouse fibroblast cells was also investigated using the patch-clamp technique. In addition, the effects of the isomers on a lipid chain-melting phase transition were determined.

Results

The EC50 concentrations for general anesthesia for the R(+) and S(-) isomers were 3.4 +/- 0.1 microM and 57 +/- 1 microM, with slopes of n = 1.9 +/- 0.1 and n = 2.9 +/- 0.2, respectively. The R(+) isomer was also much more effective than the S(-) isomer at potentiating GABA-induced currents, although the degree of stereoselectivity varied with anesthetic concentration. R(+) etomidate potentiated the GABA-induced currents by increasing the apparent affinity of GABA for its receptor. Both isomers were equally effective at disrupting lipid bilayers.

Conclusions

These data are consistent with the idea that the GABA(A) receptor plays a central role in the actions of etomidate. Etomidate exerts its effects on the receptor by binding directly to a specific site or sites on the protein and allosterically enhancing the apparent affinity of GABA for its receptor.
Stereoselective Differences in the Vasorelaxing Effects of S(+) and R(-) Ketamine on Rat Isolated Aorta
Authors: Kanellopoulos Adriani , Lenz Gunther , Muhlbauer Bernd
Published: November 2003

Background

S(+) ketamine, because of its higher anesthetic potency and lower risk of psychotomimetic reactions, has been suggested to be superior to presently available racemic ketamine. The racemate is a direct vasodilator in vivo, and thus the authors investigated the vasorelaxing effects of ketamine enantiomers on rat aorta.

Methods

Rat isolated aortic rings with and without endothelium were contracted with 3 x 10(-7) M norepinephrine. Then 10(-5) to 3 x 10(-3) M S(+), R(-), or racemic ketamine were added cumulatively. Vascular responses to ketamine were further studied in rings pretreated with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NNLA), the adenosine triphosphate-sensitive K+ channel antagonist glibenclamide, and the L-type calcium channel blocking agent D888.

Results

Ketamine enantiomers and the racemate produced concentration-dependent vasorelaxation. The relaxing effect of S(+) ketamine was significantly weaker compared with R(-) ketamine and the racemate reflected by the half-maximum effective concentration (EC50) values of 11.6 x 10(-4), 4.8 x 10(-4), and 6 x 10(-4) M, respectively. Removal of the endothelium and NNLA or glibenclamide pretreatment did not significantly alter the vasorelaxing effect of ketamine. In contrast, D888 pretreatment significantly shifted the concentration-effect curves of both S(+) and R(-) ketamine rightward (EC50 values of 18.9 x 10(-4) and 8.5 x 10(-4) M, respectively), whereas the difference between the isomers was not affected.

Conclusions

Vasorelaxation by ketamine enantiomers is quantitatively stereoselective: The effect of S(+)ketamine is significantly weaker compared with that of the racemate and R(-) ketamine. This stereoselective difference is not due to nitric oxide release, activation of adenosine triphosphate-sensitive potassium channels, or differential inhibition of L-type calcium channels.
Is Calcium a Coronary Vasoconstrictor In Vivo?
Authors: Crystal George J. , Zhou Xiping , Salem Ramez M.
Published: November 2003

Background

Calcium produces constriction in isolated coronary vessels and in the coronary circulation of isolated hearts, but the importance of this mechanism in vivo remains controversial.

Methods

The left anterior descending coronary arteries of 20 anesthetized dogs whose chests had been opened were perfused at 80 mmHg. Myocardial segmental shortening was measured with ultrasonic crystals and coronary blood flow with a Doppler flow transducer. The coronary arteriovenous oxygen difference was determined and used to calculate myocardial oxygen consumption and the myocardial oxygen extraction ratio. The myocardial oxygen extraction ratio served as an index of effectiveness of metabolic vasodilation. Data were obtained during intracoronary infusions of CaCl2 (5, 10, and 15 mg/min) and compared with those during intracoronary infusions of dobutamine (2.5, 5.0, and 10.0 microg/min).

Results

CaCl2 caused dose-dependent increases in segmental shortening, accompanied by proportional increases in myocardial oxygen consumption. Although CaCl2 also increased coronary blood flow, these increases were less than proportional to those in myocardial oxygen consumption, and therefore the myocardial oxygen extraction ratio increased. Dobutamine caused dose-dependent increases in segmental shortening and myocardial oxygen consumption that were similar in magnitude to those caused by CaCl2. In contrast to CaCl2, however, the accompanying increases in coronary blood flow were proportional to the increases in myocardial oxygen consumption, with the result that the myocardial oxygen extraction ratio remained constant.

Conclusions

Calcium has a coronary vasoconstricting effect and a positive inotropic effect in vivo. This vasoconstricting effect impairs coupling of coronary blood flow to the augmented myocardial oxygen demand by metabolic vascular control mechanisms. Dobutamine is an inotropic agent with no apparent direct action on coronary resistance vessels in vivo.
Benzodiazepines Differentially Inhibit Phenylephrine-induced Calcium Oscillations in Pulmonary Artery Smooth Muscle Cells
Authors: Hong Sung Jin , Damron Derek S. , Murray Paul A.
Published: November 2003

Background

Modulation of intracellular free calcium is a critical determinant of vasomotor tone. The authors investigated the effects of three benzodiazepines on alpha-adrenergic-induced oscillations in intracellular free calcium in individual pulmonary artery smooth muscle cells.

Methods

Pulmonary artery smooth muscle cells were cultured from explants of canine intrapulmonary artery. Fura-2-loaded pulmonary artery smooth muscle cells were continuously superfused with phenylephrine (10 microM) at 37 degrees C on the stage of an inverted fluorescence microscope. Intracellular free calcium was measured using a dual wavelength spectrofluorometer. After establishment of steady-state intracellular free calcium oscillations induced by phenylephrine, lorazepam, diazepam, or midazolam was added to the superfusate. The amplitude and frequency of the intracellular free calcium oscillations were compared before and after addition of each agent.

Results

Resting mean +/- SEM values of intracellular free calcium were 68 +/- 8 nM. Phenylephrine stimulated dose-dependent oscillations in intracellular free calcium, which reached a peak concentration of 676 +/- 35 nM and a frequency of 1.08 +/- 0.1 transients/min. Addition of lorazepam (1 microM) inhibited (P < 0.05) the amplitude (591 +/- 32 nM) but not the frequency (0.97 +/- 0.1 transients/min) of the oscillations. Conversely, diazepam (1 microM) decreased (P < 0.05) the frequency (0.79 +/- 0.1 transients/min) but not the amplitude (663 +/- 37 nM) of the oscillations. These effects were dose-dependent. In contrast, midazolam (1-30 microM) had no effect on the amplitude or frequency of intracellular free calcium oscillations. At concentrations higher than 100 microM, however, all three benzodiazepines inhibited both the amplitude and frequency of the intracellular free calcium oscillations.

Conclusion

Lorazepam and diazepam but not midazolam exerted differential inhibitory effects on phenylephrine-induced intracellular free calcium oscillations. Benzodiazepines may alter the pulmonary vascular response to sympathetic alpha-adrenoreceptor activation by direct inhibition of intracellular free calcium signaling in pulmonary artery smooth muscle cells.
Meperidine and Alfentanil Do Not Reduce the Gain or Maximum Intensity of Shivering
Authors: Ikeda Takehiko , Sessler Daniel I. , Tayefeh Farzin , Negishi Chiharu , Turakhia Minang , Marder Danielle , Bjorksten Andrew R. , Larson Merlin D.
Published: November 2003

Background

Thermoregulatory shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core temperature deviation), and maximum intensity. Meperidine (a combined mu- and kappa-agonist) treats shivering better than equianalgesic doses of pure mu-opioid agonists. Meperidine's special antishivering action is mediated, at least in part, by a disproportionate decrease in the shivering threshold. That is, meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold, whereas alfentanil (a pure mu-agonist) decreases the vasoconstriction and shivering thresholds comparably. However, reductions in the gain or maximum shivering intensity might also contribute to the clinical efficacy of meperidine. Accordingly, we tested the hypothesis that meperidine reduces the gain and maximum intensity of shivering much more than alfentanil does.

Methods

Ten volunteers were each studied on three separate days: (1) control (no drug); (2) a target total plasma meperidine concentration of 1.2 microg/ml; and (3) a target plasma alfentanil concentration of 0.2 microg/ml. Skin temperatures were maintained near 31 degrees C, and core temperatures were decreased by central-venous infusion of cold lactated Ringer's solution until maximum shivering intensity was observed. Shivering was evaluated using oxygen consumption and electromyography. A sustained increase in oxygen consumption identified the shivering threshold. The gain of shivering was calculated as the slope of the oxygen consumption versus core temperature regression, and as the slope of electromyographic intensity versus core temperature regression.

Results

Meperidine and alfentanil administration significantly decreased the shivering thresholds. However, neither meperidine nor alfentanil reduced the gain of shivering, as determined by either oxygen consumption or electromyography. Opioid administration also failed to significantly decrease the maximum intensity of shivering.

Conclusions

The authors could not confirm the hypothesis that meperidine reduces the gain or maximum intensity of shivering more than alfentanil does. These results suggest that meperidine's special antishivering effect is primarily mediated by a disproportionate reduction in the shivering threshold.
The Self-inflating Bulb to Detect Esophageal Intubation during Emergency Airway Management
Authors: Kasper Carol L. , Deem Steven
Published: November 2003

Background

The negative-pressure test using a self-inflating bulb (SIB) during emergency intubation was studied to determine its reliability and predictive value in this setting.

Methods

The endotracheal tube (ETT) position was tested in 300 consecutive patients undergoing in-hospital emergency endotracheal intubation. Immediately after intubation and before ETT cuff inflation, the following protocol was strictly followed: (1) an SIB was compressed, connected to the ETT, and released. A 10-s period was allowed for the bulb to inflate. (2) The ETT cuff was inflated, and the ETT position was confirmed using colorimetric or infrared carbon dioxide detection, or both, combined with clinical evaluation.

Results

There were 19 esophageal intubations (6% incidence). The SIB correctly identified all patients with esophageal intubation (sensitivity, 100%) and correctly identified all but three ETTs placed in the trachea (specificity, 99%). The three tracheally placed tubes that were misidentified by the bulb syringe occurred during one case each of chronic obstructive pulmonary disease, copious secretions, and obesity; of note were three tracheally placed tubes that were misidentified by the carbon dioxide analyzers during cardiopulmonary resuscitation.

Conclusions

The SIB proved to be a sensitive and specific test for esophageal intubation in the emergency setting when used according to the protocol described, and it is complementary to carbon dioxide detection. The predictive value of the bulb syringe appears to be improved when a prolonged period for reinflation is allowed. It holds particular promise because of its low cost and portability.
Sex-related Differences in the Influence of Morphine on Ventilatory Control in Humans
Authors: Dahan Albert MD , Sarton Elise , Teppema Luc , Olievier Cees
Published: November 2003

Background

Opiate agonists have different analgesic effects in male and female patients. The authors describe the influence of sex on the respiratory pharmacology of the mu-receptor agonist morphine.

Methods

The study was placebo-controlled, double-blind, and randomized. Steady-state ventilatory responses to carbon dioxide and responses to a step into hypoxia (duration, 3 min; oxygen saturation, approximately 82%; end-tidal carbon dioxide tension, 45 mmHg) were obtained before and during intravenous morphine or placebo administration (bolus dose of 100 microg/kg, followed by a continuous infusion of 30 microg x kg(-1) x h(-1)) in 12 men and 12 women.

Results

In women, morphine reduced the slope of the ventilatory response to carbon dioxide from 1.8 +/- 0.9 to 1.3 +/- 0.7 l x min(-1) x mmHg(-1) (mean +/- SD; P < 0.05), whereas in men there was no significant effect (control = 2.0 +/- 0.4 vs. morphine = 1.8 +/- 0.4 l x min(-1) x mmHg(-1)). Morphine had no effect on the apneic threshold in women (control = 33.8 +/- 3.8 vs. morphine = 35.3 +/- 5.3 mmHg), but caused an increase in men from 34.5 +/- 2.3 to 38.3 +/- 3 mmHg, P < 0.05). Morphine decreased hypoxic sensitivity in women from 1.0 +/- 0.5 l x min(-1) x %(-1) to 0.5 +/- 0.4 l x min(-1) x %(-1) (P < 0.05) but did not cause a decrease in men (control = 1.0 +/- 0.5 l x min(-1) x %(-1) vs. morphine = 0.9 +/- 0.5 l x min(-1) x %(-1)). Weight, lean body mass, body surface area, and calculated fat mass differed between the sexes, but their inclusion in the analysis as a covariate revealed no influence on the differences between men and women in morphine-induced changes.

Conclusions

In both sexes, morphine affects ventilatory control. However, we observed quantitative and qualitative differences between men and women in the way morphine affected the ventilatory responses to carbon dioxide and oxygen. Possible mechanisms for the observed sex differences in the respiratory pharmacology of morphine are discussed.
Awakening Propofol Concentration with and without Blood-Effect Site Equilibration after Short-term and Long-term Administration of Propofol and Fentanyl Anesthesia
Authors: Kazama Tomiei , Ikeda Kazuyuki , Morita Koji , Sanjo Yoshimitsu
Published: November 2003

Background

The propofol awakening concentration can vary. However, the effect site awakening propofol concentration will be a fixed value. The purpose of this study was to determine the awakening propofol concentrations obtained from infusion Schede using abrupt discontinuation of propofol (half-maximal effective concentration [EC50]) or a descending decrease in concentration to allow blood-effect site equilibration (EC50eq).

Methods

Patients undergoing short-term (group 1) and long-term (group 2) elective surgery were anesthetized with computer-assisted continuous infusion of propofol and fentanyl, with both groups receiving the same propofol (3 microg/ml) and fentanyl (1 ng/ml) concentrations 20-30 min before the end of surgery until the end. Then both groups were further divided into two subgroups: subgroup A abrupt discontinuation, and subgroup B descending concentrations of propofol (15-min duration per concentration). In the A subgroups, the response to verbal command was evaluated every 30 s. In the B subgroups, the blood propofol concentrations just permitting and just preventing response to command were averaged individually. The EC50 and EC50eq values were determined by probit analysis.

Results

The EC50 of group 1A was 1 microg/ml, which was significantly less than the 1.6 microg/ml of group 2A (P < 0.05). The awakening time of group 1A was 5.2 +/- 1.8 min, which was significantly shorter than the 9.3 +/- 3.5 min of group 2A (means +/- SD). The EC50eq of both groups 1B and 2B was 2.2 microg/ml.

Conclusions

The EC50eq was independent of propofol infusion length, compared with the EC50. Thus the potential for hysteresis during emergence from propofol anesthesia was confirmed.
Open-lung Biopsy in Patients with Acute Respiratory Distress Syndrome
Authors: Papazian Laurent , Thomas Pascal , Bregeon Fabienne , Garbe Louise , Zandotti Christine , Saux Pierre , Gaillat Francoise , Drancourt Michel , Auffray Jean-Pierre , Gouin Francois
Published: November 2003

Background

It has been suggested that fibrosis present during the fibroproliferative phase of acute respiratory distress syndrome (ARDS) can be treated by corticosteroids. However, neither clinical nor microbiologic criteria permit differentiation of this fibroproliferative phase from a nosocomial pneumonia. The aim of this observational case series was to evaluate the safety and utility of open-lung biopsy (OLB) performed in patients receiving ventilatory support who had persistent ARDS despite negative bacterial cultures.

Methods

During a 4-yr period, 37 OLBs were performed in 36 of 197 patients receiving ventilatory support who had ARDS. The severity of ARDS was assessed by a lung injury score of 3.1 +/- 0.4 (mean +/- SD) and a median ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of 118 mmHg. Histologic examination; bacterial, fungal, and acid-fast staining; and cultures of the tissue sample were performed.

Results

Fibrosis was present in only 41% of the lung specimens obtained by OLB. Only six patients received corticosteroids (17%). In 9 of the 15 patients with fibrosis, cytomegalovirus pneumonia precluded the use of corticosteroids. Histologic cytomegalovirus pneumonia was diagnosed in 18 cases. Histologic bacterial or mycobacterial pneumonia was diagnosed in five cases. No significant change in arterial blood gases was noted as linked to the biopsy procedure except an increase of the PaO2/FiO2 ratio. One pneumothorax was diagnosed on a chest roentgenogram 12 h after OLB. Only one patient required blood transfusion during the 48-h period after OLB (for an hemothorax). Five patients had moderate air leaks from operative chest tubes for 2-10 days.

Conclusions

Open lung biopsy appeared to be a useful and acceptably safe diagnostic technique in patients with ARDS. It permitted the diagnosis of unexpected cytomegalovirus pneumonia.
The Effect of the Reduction of Colloid Reduction of Oncotic Pressure, with and without Reduction of Osmolality, on Post-traumatic Cerebral Edema
Authors: Drummond John C. , Patel Piyush M. , Cole Daniel J. , Kelly Paul J.
Published: November 2003

Background

It has been asserted that reduction of colloid oncotic pressure (COP) can aggravate traumatic brain edema. To explore this issue, the authors measured the effect of COP reduction, with and without a simultaneous decrease in osmolality, on the development of brain edema after fluid percussion injury (FPI).

Methods

Isoflurane-anesthetized Wistar rats received a 2.7-atm right parasagittal FPI followed by isovolemic exchange with (1) normal saline (NS); (2) half-normal saline (0.5 NS); (3) whole blood (WB); or (4) hetastarch (Hespan, Dupont). Shed blood (16 ml) was replaced with donor erythrocytes suspended in the study fluid. The WB group received heparinized fresh donor WB. Central venous pressure was maintained with additional study fluid as required. The specific gravity (SG) of the cortex and subcortex near the impact site was determined 4.5 h after FPI. The water content of the hemispheres was also determined using the wet-dry method. To define the status of the blood-brain barrier in the non-FPI hemisphere, two additional groups (FPI, non-FPI) were studied. Both groups received 30 mg/kg Evans' blue and NS at 4 ml/kg(-1)/h(-1). Four hours after FPI, the concentration of Evans' blue in the hemispheres was determined.

Results

After exchange, COP (mmHg +/- SD) decreased in the NS (9.6 +/- 2.1) and 0.5 NS (8.5 +/- 0.5) groups and was unchanged in the WB (16.7 +/- 3.3) and hetastarch (18.9 +/- 1.1) groups. Osmolality was unchanged in the WB group (295 +/- 5 mOsm/kg), increased in the NS (304 +/- 3 mOsm/kg) and hetastarch (306 +/- 2 mOsm/kg) groups, and was decreased in the 0.5 NS group (261 +/- 6 mOsm/kg). The Evans' blue data indicated that FPI resulted in blood-brain barrier damage in both hemispheres. In all four exchange groups, the SG of both cortical and subcortical tissue was less (indicating greater water content) in the impact hemisphere than in the nonimpact hemisphere. The SG was less in both hemispheres, although it was less in both hemispheres in the NS and 0.5 NS groups than in the WB and hetastarch groups. The lowest SG values were observed in the 0.5 NS group. The wet-dry water content determinations yielded a similar pattern of edema formation.

Conclusions

These data, while confirming the important edematogenic effect of decreased osmolality, indicate that COP reduction per se can also aggravate brain edema after a mild to moderate mechanical head injury.
Pulmonary Vasodilator Response to Adenosine Triphosphate-Sensitive Potassium Channel Activation Is Attenuated during Desflurane but Preserved during Sevoflurane Anesthesia Compared with the Conscious State
Authors: Nakayama Masayasu , Kondo Uruo , Murray Paul A.
Published: November 2003

Background

The objective of this study was to investigate the effects of sevoflurane and desflurane anesthesia on the pulmonary vasodilator response to the adenosine triphosphate-sensitive potassium channel agonist, lemakalim, compared with the response measured in the conscious state. In addition, the authors assessed the extent to which sympathetic alpha1-adrenoreceptor inhibition and cyclooxygenase pathway inhibition modulate the vasodilator response to lemakalim.

Methods

Twenty-four conditioned male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow relationship. After preconstriction with the thromboxane analogue, U46619, dose-response relationships to lemakalim were assessed on separate days in the conscious state and during sevoflurane (approximately 3.5% end-tidal) and desflurane (approximately 10.5% end-tidal) anesthesia (approximately 1.5 minimum alveolar concentration for each anesthetic agent). The effects of sympathetic alpha1-adrenoreceptor inhibition (prazosin) and cyclooxygenase inhibition (indomethacin) on the pulmonary vasodilator response to lemakalim also were assessed in the conscious and desflurane-anesthetized states.

Results

Neither sevoflurane nor desflurane had a net effect on the baseline left pulmonary vascular pressure-flow relationship compared with the conscious state. The magnitude of the pulmonary vasodilator response to lemakalim was preserved during sevoflurane anesthesia but was attenuated (P < 0.05) during desflurane anesthesia compared with the conscious state. The attenuated lemakalim-induced vasodilator response during desflurane anesthesia was partially reversed (P < 0.05) by pretreatment with prazosin but not indomethacin.

Conclusion

These results indicate that adenosine triphosphate-sensitive potassium channel-mediated pulmonary vasodilation is preserved during sevoflurane anesthesia but is attenuated during desflurane anesthesia. The attenuated response to adenosine triphosphate-sensitive potassium channel activation during desflurane anesthesia is partially mediated by reflex sympathetic alpha1-adrenoreceptor vasoconstriction.
Effect of Subarachnoid Bupivacaine Block on Anesthetic Requirements for Thiopental in Rats
Authors: Eappen Sunil , Kissin Igor
Published: November 2003

Background

Subarachnoid bupivacaine blockade has been reported to reduce thiopental and midazolam hypnotic requirements in patients. The purpose of this study was to examine if local anesthetically induced lumbar intrathecal blockade would reduce thiopental requirements for blockade of motor responses to noxious and nonnoxious stimuli in rats.

Methods

After intrathecal and external jugular catheter placement, rats were assigned randomly to two groups in a crossover design study, with each rat to receive either 10 microl of 0.75% bupivacaine or 10 microl of normal saline intrathecally. The doses of intravenously administered thiopental required to ablate the eyelid reflex, to block the withdrawal reflex of a front limb digit, and to block the corneal reflex were compared. In two separate groups of animals, hemodynamic parameters and concentrations of thiopental in the brain were compared between intrathecally administered bupivacaine and saline.

Results

The thiopental dose required to block the described responses was decreased with intrathecally administered bupivacaine versus intrathecally administered saline from (mean +/- SD) 40 +/- 5 to 24 +/- 4 mg/kg (P < 0.001) for the eyelid reflex, from 51 +/- 6 to 29 +/- 6 mg/kg (P < 0.005) for front limb withdrawal, and from 67 +/- 8 to 46 +/- 8 mg/kg (P < 0.01) for the corneal reflex. The concentration of thiopental in the brain at the time of corneal reflex blockade for the group given bupivacaine was significantly lower than in the group given saline (24.1 vs. 35.8 microg/g, P = 0.02).

Conclusion

This study demonstrates that lumbar intrathecally administered local anesthetic blockade decreases anesthetic requirements for thiopental for a spectrum of end points tested. This effect is due neither to altered pharmacokinetics nor to a direct action of the local anesthetic on the brain; rather, it is most likely due to decreased afferent input.
Interaction of Isoflurane and Sevoflurane with α- and β-adrenoceptor Stimulations in Rat Myocardium
Authors: Hanouz Jean-Luc , Gueugniaud Pierre-Yves , Lecarpentier Yves , Coriat Pierre , Riou Bruno
Published: November 2003

Background

Halothane potentiates the positive inotropic effects of alpha- and beta-adrenoceptor stimulations but impairs the positive lusitropic effect of beta-adrenoceptor stimulations. However, the interactions of isoflurane and sevoflurane with alpha- and beta-adrenoceptor stimulation have not been entirely defined.

Methods

The effects of 1 minimum alveolar concentration isoflurane and sevoflurane on the inotropic responses induced by phenylephrine (10(-8) to 10(-4) M) or isoproterenol (10(-8 to 10(-4) M) were studied in rat left ventricular papillary muscles in vitro (Krebs-Henseleit solution, 29 degrees C; pH, 7.4; 0.5 mM calcium; stimulation frequency, 12 pulses/min). The positive lusitropic effects of alpha- and beta-adrenoceptor stimulations were studied under isotonic and isometric conditions. Data are mean percentages of baseline +/- SEM.

Results

In control groups, phenylephrine (134 +/- 8%; P < 0.05) and isoproterenol (171 +/- 7%; P < 0.05) induced a positive inotropic effect. Isoflurane enhanced the positive inotropic effects of phenylephrine (185 +/- 10%; P < 0.05) and of isoproterenol (203 +/- 11%; P < 0.05). Sevoflurane enhanced the positive inotropic effects of phenylephrine (187 +/- 10%; P < 0.05) and of isoproterenol (228 +/- 11%; P < 0.05). These potentiations were similar to those previously reported with halothane. Isoflurane and sevoflurane did not modify the positive lusitropic effects under low and high loads of isoproterenol.

Conclusion

Although isoflurane and sevoflurane have moderate negative inotropic effects, they potentiated the positive inotropic effects of alpha- and beta-adrenoceptor stimulations but did not modify the positive lusitropic effects of beta-adrenoceptor stimulation.
Proarrhythmic and Antiarrhythmic Effects of Bupivacaine in an In Vitro Model of Myocardial Ischemia and Reperfusion
Authors: Picard Sandra , Rouet Rene , Flais Frederic , Ducouret Pierre , Babatasi Gerard , Khayat Andre , Potier Jean-Claude , Bricard Henri , Gerard Jean-Louis
Published: November 2003

Background

Bupivacaine may have toxic cardiovascular effects when accidentally administered by intravascular injection. However, its electrophysiologic effects in the presence of myocardial ischemia remain unknown. The authors evaluated the electrophysiologic and anti- and proarrhythmic effects of bupivacaine in an in vitro model of the ischemic and reperfused myocardium.

Methods

In a double-chamber bath, a guinea pig right ventricular muscle strip was subjected partly to normal conditions and partly to simulated ischemia followed by reperfusion. The electrophysiologic effects of bupivacaine were studied at 1, 5, and 10 microM concentrations.

Results

Bupivacaine (5 and 10 microM) decreased the maximal upstroke velocity of the action potential (Vmax) in normoxic conditions and further decreased (10 microM) the Vmax decrease induced by ischemic conditions. Bupivacaine reduced the mean occurrence time to the onset of myocardial conduction blocks (9 +/- 3 min; mean +/- SD; P < 0.005 with 5 and 10 microM, compared with 17 +/- 6 min during simulated ischemia with no drug or control), and it increased the number of preparations that became inexcitable to pacing (55% of preparations, with 1 microM and 100% with 5 and 10 microM, compared with 17% for the control group). The incidence of spontaneous arrhythmias was reduced by 5 and 10 microM bupivacaine during ischemia and reperfusion and was enhanced by 1 microM bupivacaine during the ischemic phase.

Conclusions

In guinea pig myocardium under ischemic conditions, bupivacaine induced a loss of excitability at concentrations of 5 and 10 microM. Proarrhythmic effects observed at 1 microM were considered as lower than the cardiotoxic range in normoxic conditions. The incidence of reperfusion arrhythmias was decreased at all concentrations.
Intravenous Remifentanil
Authors: Kan Randall E. , Hughes Samuel C. , Rosen Mark A. , Kessin Charlize , Preston Paul G. , Lobo Errol P.
Published: November 2003

Background

Remifentanil has not been studied in obstetric patients. This study evaluates the placental transfer of remifentanil and the neonatal effects when administered as an intravenous infusion.

Methods

Nineteen parturients underwent nonemergent cesarean section with epidural anesthesia and received 0.1 microg kg(-1) x min(-1) remifentanil intravenously, which was continued until skin closure. Maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood samples were obtained at delivery for analysis of drug concentrations of remifentanil, its metabolite, and blood gases. Maternal vital signs were monitored continuously, and pain and sedation levels were assessed intermittently. Apgar scores were obtained at 1, 5, 10, and 20 min, and Neonatal and Adaptive Capacity Scores were noted 30 and 60 min after delivery. Parturients and newborns were observed for at least 24 h after surgery for side effects.

Results

The means and SDs of UV:MA and UA:UV ratios for remifentanil were 0.88+/-0.78 and 0.29+/-0.07, respectively. Mean clearance was 93 ml x min(-1) kg(-1). The mean UV:MA and UA:MV ratios for remifentanil acid were 0.56+/-0.29 and 1.23+/-0.89, respectively. The mean MA (remifentanil acid):MA (remifentanil) ratio was 2.92+/-3.65. There were no adverse effects on the neonates, but there was a sedative effect and respiratory depressant effect on the mothers.

Conclusions

Remifentanil crosses the placenta but appears to be rapidly metabolized, redistributed, or both. Maternal sedation and respiratory changes occur, but without adverse neonatal or maternal effects.
A Comparison of the Posterior versus Lateral Approaches to the Block of the Sciatic Nerve in the Popliteal Fossa
Authors: Hadzic Admir , Vloka Jerry D.
Published: November 2003

Background

The main disadvantage of the posterior approach to the block of the sciatic nerve in the popliteal fossa (popliteal block [PB]) is the need to place the patient in the prone position. In this study, the authors examined the clinical utility of a recently described lateral approach to PB that is performed with the patient in the supine position, and they compared its ability to provide reliable surgical anesthesia with that of the posterior approach.

Methods

Fifty patients undergoing surgery of a lower extremity were randomized to receive the PB using either the lateral (n=25) or the posterior approach (n=25). With both techniques, 40 ml 1.5% alkalinized mepivacaine with 1:200,000 epinephrine were injected on successful nerve localization using low current output nerve stimulation.

Results

There were no differences in American Society of Anesthesiologists physical status or demographic data between the groups (ASA status, I-III; mean age, 50+/-15 yr; 27 men, 23 women). All patients had good intraoperative analgesia, except one in the lateral group, who reported pain outside the distribution of the sciatic nerve.

Conclusions

Although blockade using the lateral approach took longer to accomplish, both techniques resulted in clinically acceptable anesthesia in the distribution of the sciatic nerve.
Labor Epidural Analgesia without an Intravascular “Test Dose”
Authors: Norris Mark C. , Fogel Steven T. , Dalman Hiroko , Borrenpohl Susan , Hoppe William , Riley Alicia
Published: November 2003

Background

This study prospectively evaluated the ability of aspiration to detect intravascular placement of multiple-orifice epidural catheters.

Methods

Multiple-orifice, 20-gauge epidural catheters were inserted in 1,029 laboring women. Catheters were observed and aspirated for blood or cerebrospinal fluid before they were tested with 2 ml local anesthetic. If the results of this test were negative (no spinal anesthesia), the authors induced and maintained labor analgesia with a dilute local anesthetic and opioid solution. Patients with bilateral sensory change and effective labor analgesia had a "positive" epidural catheter. Women with unilateral block, inadequate analgesia despite some sensory change or those who delivered before being adequately assessed had "equivocal" catheters. Patients with neither analgesia nor sensory change had "negative" catheters.

Results

Aspiration and observation identified 60 intravenously placed catheters. Six catheters, which were placed initially in a blood vessel, were withdrawn until aspiration was negative, and then the anesthetic was infused. Four of these catheters were positive and two were still positioned intravascularly. Two other catheters may have been intravenously placed despite negative results of aspiration. The incidence of false-negative results of aspiration was 0 to 2 of 1,085 (upper limit of 95% CI, 0.2% to 0.4%). No patient showed any signs or symptoms of local anesthetic toxicity.

Conclusions

Under the conditions of this study, which include using multiple-orifice catheters and dilute solutions of local anesthetic and opioid, aspiration and incremental drug injection alone safeguard against the risks of intravenously positioned local anesthetics. These results should not be extrapolated to other clinical settings without further study.
Effects of Oral Clonidine on Heart Rate Changes after Neostigmine-Atropine Administration
Authors: Kimura Tetsu , Tanaka Makoto , Nishikawa Toshiaki
Published: November 2003

Background

Clonidine reduces heart rate (HR) responses to atropine, whereas neostigmine causes bradycardia. This study was designed to determine whether clonidine premedication would reduce tachycardia after neostigmine-atropine administration.

Methods

Fifty adult patients without cardiovascular disorders who were scheduled for elective surgeries were randomly assigned to receive approximately 5 microg/kg (oral clonidine clonidine group, n=25) or no clonidine (control group, n=25) 90 min before induction of general anesthesia. After tracheal intubation, anesthesia was maintained with N2O and 12% isoflurane in oxygen while patients were paralyzed with vecuronium and mechanically ventilated. When surgeries were completed, adequate spontaneous respiration, responses to verbal commands, and sustained tetanus by stimulating the ulnar nerve were confirmed, and patients' tracheas were extubated. Then a mixture of 0.05 mg/kg neostigmine and 0.02 mg/kg atropine was administered intravenously over 20 s under stable hemodynamic condition (systolic blood pressure and HR within +/-5% of preceding values), and blood pressure and HR were measured noninvasively at 1-min intervals for 10 min.

Results

Increases in HR in the clonidine group were significantly less 1-4 min after neostigmine--atropine injections compared with HR values in the control group. A maximum increase in HR of the clonidine group was also significantly less than the control group (15+/-7 vs. 23+/-10 beats/min; means+/-SD), whereas absolute values of mean blood pressure were similar. Severe bradycardia (HR < 50 beats/min) developed in no patients in either group.

Conclusions

Premedication with 5 microg/kg oral clonidine attenuates the initial increases in HR without subsequent decreases in HR.