bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose-Range Effects of Clonidine Added to Lidocaine for Brachial Plexus Block
Authors: Bernard Jean-Marc , Macaire Philippe 
Published: November 2003

Background
Although addition of clonidine to local anesthetics can prolong pain relief after peripheral nerve block, a dose-range effect has not been determined.

Methods
Fifty-six outpatients undergoing carpal tunnel release were randomly assigned to receive in a double-blind fashion 45 ml of a mixture containing either 400 mg lidocaine plus saline or 400 mg lidocaine plus 30, 90 or 300 microg clonidine for axillary nerve block. In each group (n = 14), blocks were evaluated at regular time intervals to determine sensory and motor functions in the five nerve regions of the hand and forearm. Also, adequacy of the block for surgery, postoperative pain intensity, and side effects were evaluated.

Results
Compared with saline, each dose of clonidine reduced the onset time of sensory block and extended the field of adequate anesthesia. Ten minutes after injection, 30 microg clonidine was more effective than 90 microg clonidine in producing sensory blockade. Sedation occurred with clonidine 30 and 300 microg. Clonidine reduced the use of supplementary intravenous anesthetic agents for surgery and produced dose-dependent prolongation of analgesia, reaching a mean 770 min (range, 190-1440 min) for the largest dose. Clonidine also produced a dose-dependent decrease in systolic arterial pressure of up to -22.5% (range, -6.0 29.9%) of baseline. With clonidine, 300 microg, three patients had mean arterial pressure of <55 mmHg; four patients had episodes of arterial oxyhemoglobin saturation of <90%, and two others were not discharged because of hypotension.

Conclusion
This study suggests that a small dose of clonidine enhances the quality of the peripheral blocks from lidocaine and limits the classical alpha2-agonist side effects to sedation.
Oral Clonidine Premedication Does Not Alter the Efficacy of Simulated Intravenous Test Dose Containing Low Dose Epinephrine in Awake Volunteers
Authors: Tanaka Makoto , Nishikawa Toshiaki 
Published: November 2003

Background
Clonidine premedication modifies the hemodynamic responses to sympathomimetics. The present study was designed to test whether clonidine altered the response to a small intravenous dose of epinephrine, such as that which might be used in an epidural test dose.

Methods
In 18 healthy volunteers, four series of determinations were performed in random order and were separated by a minimum 72 h: (1) no premedication followed by intravenous saline 3 ml, (2) no premedication followed by intravenous test dose containing 3 ml of 1.5% lidocaine + 15 microg epinephrine, (3) oral clonidine (5 microg/kg 1.5 h before hemodynamic determinations) followed by intravenous saline, and (4) oral clonidine followed by intravenous epinephrine-containing test dose. Systolic blood pressure (SBP) and heart rate (HR) were measured continuously, and symptoms associated with central nervous system toxicity were noted.

Results
After the test dose injections, HR and SBP increased with or without clonidine premedication. The 95% confidence intervals for the maximum HR increases with and without clonidine were 49-61 and 44-54 beats/min, respectively, indicating that one could not be absolutely certain that everyone would develop a positive HR response. The HR increase was > or = 20 beats/min in 18 of 18 volunteers given epinephrine with or without clonidine and in 0 of 18 volunteers given saline. Calculated sensitivities, specificities, and positive and negative predictive values were all 100% based on the conventional HR criterion and were unaltered by clonidine. Subjective symptoms were not affected by clonidine.

Conclusions
Oral clonidine does not alter the efficacy of epinephrine-containing test doses used for detecting intravascular injection.
Physiologic Determinants of the Response to Inhaled Nitric Oxide in Patients with Acute Respiratory Distress Syndrome
Authors: Manktelow Claire , Bigatello Luca M. , Hess Dean , Hurford William E. 
Published: November 2003

Background
The response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) varies. It is unclear which patients will respond favorably and whether the initial response persists over time. The authors defined a clinically useful response to inhaled NO as an increase of more than 20% of the ratio of the partial pressure of oxygen (Pa(O2)) to the inspiratory fraction of oxygen (FIO2), a decrease of more than 20% of pulmonary vascular resistance, or both. The authors hypothesized that patients who initially respond favorably are likely to show persistent improvements of gas exchange and hemodynamics after 48 h of NO inhalation.

Methods
The medical records and collected research data of 88 patients with ARDS who received 92 trials of NO inhalation between March 1991 and February 1996 were reviewed.

Results
Fifty-three of the 92 trials (58%) produced a clinically significant response to NO. In the responding patients who continued to receive NO therapy (n = 43), the Pa(O2)/FiO2 ratio remained higher (120 +/- 46 vs. 89 +/- 32 mmHg before NO; P < 0.01) and the mean pulmonary artery pressure remained lower (35 +/- 8 vs. 40 +/- 12 mmHg before NO; P < 0.01) at 48 h. Only 33% of the patients with septic shock responded to inhaled NO compared with 64% of those without septic shock (P < 0.02).

Conclusions
Most patients with ARDS had clinically useful responses to NO inhalation. Patients with an initial favorable response maintained the improvement at 48 h. Patients with septic shock were less likely to respond favorably.
High Carboxyhemoglobin Concentrations Occur in Swine during Desflurane Anesthesia in the Presence of Partially Dried Carbon Dioxide Absorbents
Authors: Frink Edward J. , Nogami Wallace M. , Morgan Scott E. , Salmon Roger C. 
Published: November 2003

Background
Increased carboxyhemoglobin concentrations in patients receiving inhalation anesthetics (desflurane, enflurane, and isoflurane) have been reported. Recent in vitro studies suggest that dry carbon dioxide absorbents may allow the production of carbon monoxide.

Methods
The authors used high fresh oxygen flow (5 or 10 l/min) through a conventional circle breathing system of an anesthesia machine for 24 or 48 h to produce absorbent drying. Initial studies used 10 l/min oxygen flow with the reservoir bag removed or with the reservoir bag left in place during absorbent drying (this increases resistance to gas flow through the canister). A third investigation evaluated a lower flow rate (5 l/min) for absorbent drying. Water content of the absorbent and temperature were measured. Pigs received a 1.0 (human) minimum alveolar concentration desflurane anesthetic (7.5%) for 240 min using a 1 l/min oxygen flow rate with dried absorbent. Carbon monoxide concentrations in the circuit and carboxyhemoglobin concentrations in the pigs were measured.

Results
Pigs anesthetized with desflurane using Baralyme exposed to 48 h of 10 l/min oxygen flow (reservoir bag removed) had extremely high carboxyhemoglobin concentrations (more than 80%). Circuit carbon monoxide concentrations during desflurane anesthesia using absorbents exposed to 10 l/min oxygen flow (reservoir bag removed, 24 h) reached peak values of 8,800 to 13,600 ppm, depending on the absorbent used. Carboxyhemoglobin concentrations reached peak values of 73% (Baralyme) and 53% (soda lime). The water content of Baralyme decreased from 12.1 +/- 0.3% (mean +/- SEM) to as low as 1.9 +/- 0.4% at the bottom of the lower canister (oxygen flow direction during drying was from bottom to top). Absorbent temperatures in the bottom canister increased to temperatures as high as 50 degrees C. With the reservoir bag in place during drying (10 l/min oxygen flow), water removal from Baralyme was insufficient to produce carbon monoxide (lowest water content = 5.5%). Use of 5 l/min oxygen flow (reservoir bag removed) for 24 h did not reduce water content sufficiently to produce carbon dioxide with desflurane.

Conclusions
An oxygen flow rate of 10 l/min for 24 h in a conventional anesthesia circuit can dry carbon dioxide absorbents sufficiently to produce extremely high levels of carbon monoxide with high carboxyhemoglobin concentrations in desflurane-anesthetized pigs. When the reservoir bag is in place on the anesthesia machine or when a lower oxygen flow rate (5 l/min) is used, carbon dioxide absorbent drying still occurs, but 24-48-h exposure time is insufficient to allow for carbon monoxide production with desflurane.
Isobolographic Analysis of Interactions between Intravenous Morphine, Propacetamol, and Diclofenac in Carrageenin-injected Rats
Authors: Fletcher Dominique , Benoist Jean-Michel , Gautron Michele , Guilbaud Gisele 
Published: November 2003

Background
It has been suggested that the combination of analgesic drugs may have additive or synergistic effects. In clinical practice, this might allow better analgesia and reduction of side effects.

Methods
The effects of analgesic drugs were studied in a model of acute inflammatory pain in carrageenin-injected rats using the vocalization threshold to paw pressure. A combination of three different intravenous drugs were used: morphine, diclofenac, and propacetamol, a pro-drug of acetaminophen. The dose-response curves were first obtained for each drug alone. The analgesic potencies of the combinations of morphine and diclofenac (ratios, 1:5.66 and 1:10), morphine and propacetamol (ratio, 1:250), and diclofenac and propacetamol (ratio, 1:65.7) were thereafter evaluated and compared with the effects of the drugs alone.

Results
For the two different ratios tested, synergy between diclofenac and morphine was observed only with the higher doses. Propacetamol and morphine or diclofenac and propacetamol combinations were additive for all doses tested.

Conclusions
This study found a synergy between intravenous morphine and diclofenac that is consistent with and helps explain the clinical value of this type of combination in the treatment of acute pain in humans.
Effect of Intravenous Anesthetics on Inward Rectifier Potassium Current in Rat and Human Ventricular Myocytes
Authors: Carnes Cynthia A. , Muir William , Van Wagoner David R. 
Published: November 2003

Background
Inhibition of the inward rectifying potassium current (I(K1)) may cause cardiac dysrhythmias by decreasing resting membrane potential or prolonging action potential.

Methods
The effects of thiopental, ketamine, and propofol on I(K1) conductance were evaluated in rat ventricular myocytes. The effect of thiopental on I(K1) conductance was also evaluated in human ventricular myocytes. Currents were recorded using the nystatin-perforated whole-cell patch-clamp technique (holding potential, -50 mV; test potentials, -140 to -40 mV). Pipette solution contained 130 mM KCl, 5 mM MgCl2, 5 mM HEPES, and 5 mM EGTA,pH 7.2. Bath solution (32 degrees C) contained 134 mM NaCI, 4 mM KCl, 1 mM MgCl2, 1 mM CaCl2, 0.3 mM CdCl2, 5 mM HEPES, and 5 mM d-glucose,pH 7.4. Drug concentrations examined encompassed the range of clinically relevant unbound plasma concentrations. Currents were normalized for cell capacitance. Conductance was calculated as current density/delta mV from -140 to -100 mV. Analysis of variance was used to test for changes in conductance as a function of drug concentration.

Results
Thiopental reduced I(K1) conductance in a concentration-dependent manner (P < 0.0001). Thiopental-induced changes in I(K1) conductance in rat ventricular myocytes were fit to an inhibitory E(max) model, with a median inhibitory concentration of 10.5 microM. The effect of thiopental on I(K1) conductance in human ventricular cells was comparable to that observed in rat ventricular myocytes. Neither ketamine nor propofol altered I(K1) conductance.

Conclusions
Thiopental reduces I(K1) conductance in a concentration-dependent manner at clinically relevant concentrations in both rat and human ventricular myocytes.
Pulmonary Blood Flow Distribution in Sheep
Authors: Walther Sten M. , Domino Karen B. , Glenny Robb W. , Hlastala Michael P. 
Published: November 2003

Background
Recent studies providing high-resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture.

Methods
Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 microm) in six sheep studied in four conditions: prone and awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data.

Results
Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to-peripheral gradient in animals breathing spontaneously (P < 0.05).

Conclusions
The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.
Effects of Blood Glucose Changes and Physostigmine on Anesthetic Requirements of Halothane in Rats
Authors: Ishizawa Yumiko , Ohta Shuichiro , Shimonaka Hiroyuki , Dohi Shuji 
Published: November 2003

Background
Although hyper- and hypoglycemia induce neurophysiologic changes, there have been no reports on the effects of blood glucose changes on anesthetic requirements. This study examined the effects of hyper- and hypoglycemia on the minimum alveolar concentration (MAC) of halothane in rats. In addition, based on a previous finding that the level of brain acetylcholine was reduced during mild hypoglycemia, the authors examined the influence of physostigmine on MAC during hypoglycemia.

Methods
In Sprague-Dawley rats, anesthesia was induced and maintained with halothane in oxygen and air. The MAC was determined by observing the response to tail clamping and tested during mild hypoglycemia (blood glucose level, 60 mg/dl) and hyperglycemia (blood glucose level, 300 and 500 mg/dl) induced by insulin and glucose infusion, respectively (experiment 1). The effects of 0.3 and 1.0 mg/kg physostigmine given intraperitoneally on MAC were examined in rats with mild and severe hypoglycemia (blood glucose level, 60 and 30 mg/dl; experiment 2).

Results
In experiment 1, mild hypoglycemia significantly reduced the MAC of halothane (0.76 +/- 0.03%) compared with the control value (0.92 +/- 0.04%), but hyperglycemia did not change MAC. In experiment 2, mild and severe hypoglycemia reduced MAC of halothane in a degree-dependent manner. Physostigmine (1 mg/kg) had no effect on MAC regardless of blood glucose level, but 0.3 mg/kg reduced MAC.

Conclusions
Hypoglycemia reduced anesthetic requirements in a degree-dependent manner, whereas hyperglycemia had no effects. Although the mechanism of hypoglycemic MAC reduction needs further investigations, physostigmine studies suggest that this may not be related to inhibition of cholinergic transmission.
Recovery and Kinetic Characteristics of Desflurane and Sevoflurane in Volunteers after 8-h Exposure, including Kinetics of Degradation Products
Authors: Eger Edmond I. , Bowland Terri , Ionescu Pompiliu , Laster Michael J. , Fang Zexu , Gong Diane , Sonner James , Weiskopf Richard B. 
Published: November 2003

Background
Desflurane and sevoflurane permit speedier changes in anesthetic partial pressures than do older halogenated anesthetics. The authors determined the kinetic characteristics of desflurane and sevoflurane and those of compound A [CH2F-O-C(=CF2)(CF3)], a nephrotoxic degradation product of sevoflurane.

Methods
Volunteers received 1.25 minimum alveolar concentration of desflurane or sevoflurane, each administered for 8 h in a fresh gas inflow of 2 l/min. Inspired (F(I)) and end-tidal (F(A)) concentrations of anesthetic and compound A were measured during administration, and F(A) relative to F(A0) (the last end-tidal concentration during administration) during elimination. The indices of recovery were also measured.

Results
The ratio F(I)/F(A) rapidly approached 1.0, with values greater for sevoflurane (desflurane 1.06 +/- 0.01 vs. sevoflurane 1.11 +/- 0.02, mean +/- SD). The ratio F(A)/F(I) for compound A was approximately 0.8. The F(A)/F(A0) ratio decreased slightly more rapidly with desflurane than with sevoflurane, and objective measures indicated faster recovery with desflurane: The initial response to command (14 +/- 4 min vs. 28 +/- 8 min [means +/- SD]) and orientation (19 +/- 4 vs. 33 +/- 9 min) was quicker, and recovery was faster as defined by results of the Digit Symbol Substitution, P-deletion, and Trieger tests. Desflurane produced less vomiting (1 [0.5, 3]; median [quartiles] episodes) than did sevoflurane (5 [2.5, 7.5] episodes). The F(A)/F(A0) ratio for compound A decreased within 5 min to a constant value of 0.1.

Conclusions
These anesthetics have kinetics consistent with their solubilities. Sevoflurane's greater biodegradation probably increases F(I)/F(A) differences during anesthetic administration and decreases F(A)/F(A0) differences during elimination. The F(A) for compound A differs from F(I) by 20% (F(A)/F(I) = 0.8) because of substantial degradation. Recovery from anesthesia proceeds nearly twice as fast with desflurane than with sevoflurane. Differences in ventilation, or alveolar or tissue elimination, do not completely explain the slower recovery with sevoflurane.
Pharmacokinetics Anesthesiologists, and Pharmacodynamics of Remifentanil in Persons with Renal Failure Compared with Healthy Volunteers
Authors: Hoke Frank J. , Shlugman David , Dershwitz Mark , Michalowski Piotr , Malthouse-Dufore Sherry , Connors Patricia M. , Martel Dave , Rosow Carl E. , Muir Keith T. , Rubin Nina , Glass Peter S. A. 
Published: November 2003

Background
Remifentanil is an opioid analgesic for use in anesthesia. An ester linkage renders it susceptible to rapid metabolism by blood and tissue esterases. Thus it was hypothesized that remifentanil elimination would be independent of renal function. Because its principal metabolite (GR90291) is eliminated renally, it would depend on renal function. This study was designed to evaluate the pharmacokinetics and pharmacodynamics of remifentanil and its metabolite in persons with and without renal failure.

Methods
Two groups of volunteers received two-stage infusions of remifentanil: low dose with 0.0125 microg x kg(-1) x min(-1) for 1 h followed by 0.025 microg x kg(-1) x min(-1) for 3 h; and high dose with 0.025 microg x kg(-1) x min(-1) for 1 h followed by 0.05 microg x kg(-1) x min(-1) for 3 h. Blood samples were collected for analysis of remifentanil and GR90291 concentrations. The pharmacokinetics of remifentanil were fit using a one-compartment pharmacokinetic model. Remifentanil's effect was determined intermittently using minute ventilation during a hypercapnic (7.5% CO2) challenge.

Results
Fifteen patients with renal failure and eight control participants were enrolled. The clearance and volume of distribution of remifentanil were not different between those with renal failure and the controls. Patients with renal failure showed a marked reduction in the elimination of GR90291; the half-life of the metabolite increased from 1.5 h in the controls to more than 26 h in patients with renal failure. The steady-state concentration of GR90291 is likely to be more than 25 times higher in persons with renal failure. There were no obvious differences in opioid effects on minute ventilation in the controls and in patients with renal failure.

Conclusions
The pharmacokinetics and pharmacodynamics of remifentanil were not altered in patients with renal disease, but the elimination of its principal metabolite, GR90291, was markedly reduced. Based on simulations, the concentration of GR90291 at the end of a 12-h remifentanil infusion of 2 microg x kg(-1) x min(-1) is not likely to produce significant opioid effects.
Characterization of Adenosine Receptors Mediating Spinal Sensory Transmission Related to Nociceptive Information in the Rat
Authors: Nakamura Isao , Ohta Yoshihiro , Kemmotsu Osamu MD 
Published: November 2003

Background
Adenosine analogs have been shown to produce antinociception after intrathecal administration. To determine the adenosine receptor subtype involved in spinal antinociception, the effects of selective agonists and an antagonist on the evoked potentials recorded from a neonatal rat spinal cord were studied. The measured potentials are a slow ventral root potential (slow VRP), which is the C-fiber-evoked excitatory response associated with nociceptive information; a monosynaptic reflex (MSR), which reflects a non-nociceptive transmission related to motor function; and a dorsal root potential (DRP), which reflects a gamma-aminobutyric acidA (GABA(A)) receptor-mediated presynaptic inhibition associated with analgesia.

Methods
The evoked potentials were recorded in response to electric stimulation of a lumbar dorsal root. Dose-response curves of agonists for these responses were obtained to determine their relative potency order. The antagonist dissociation constants (K(D) values) were estimated by Schild analysis.

Results
Adenosine agonists dose dependently inhibited the slow VRP and the MSR. However, the slow VRP was five to eight times more sensitive to them than was the MSR. The rank order of agonist potency was N6-cyclohexyladenosine (CHA) = N6-(R)-phenylisopropyladenosine (R-PIA) > 5'-N-ethylcarboxamidoadenosine (NECA) > CGS 21680 in both responses. 8-Cyclopentyltheophylline produced dose-dependent parallel shifts to the right of NECA dose-response curves for these responses. Schild analysis gave linear plots with slopes near unity. The K(D) values of CPT for the MSR and the slow VRP were estimated to be 5.5 nM and 4.3 nM, respectively. The DRP was also depressed by adenosine agonists with potency order of CHA > NECA > CGS 21680. 8-Cyclopentyltheophylline antagonized the inhibitory effects of CHA on the DRP.

Conclusions
The results indicate that adenosine agonists inhibit spinal sensory transmission related to nociception by acting at the A1 receptors. The A1 receptor also seems to be involved in transmission related to the spinal motor system. Feedback inhibition mediated by GABA(A) receptors does not contribute to this antinociceptive action.