bluuebunny/crossref_metadata_2025 huggingface dataset:
Alfentanil, but Not Amitriptyline, Reduces Pain, Hyperalgesia, and Allodynia from Intradermal Injection of Capsaicin in Humans
Authors: Eisenach James C. , Hood David D. , Curry Regina , Tong Chuanyao
Published: November 2003

Background

Intradermal injection of capsaicin produces brief pain followed by hyperalgesia and allodynia in humans, and the latter effects are mediated by spinal N-methyl-D-aspartate mechanisms. Amitriptyline recently was shown to antagonize N-methyl-D-aspartate receptors, and in this study, the authors sought to determine the effect of amitriptyline alone and with the opioid alfentanil on hyperalgesia and allodynia produced by intradermal injection of capsaicin.

Methods

Forty-six healthy volunteers in the general clinical research center received repeated intradermal injections of capsaicin (100 microg) alone or before and after systemic injection of 4 mg midazolam, 25 mg amitriptyline, alfentanil by computer-controlled infusion, or amitriptyline plus alfentanil. Acute pain and areas of mechanical hyperalgesia and allodynia were determined at specified intervals. Blood was obtained for alfentanil and amitriptyline assay.

Results

Capsaicin injection produced acute pain followed by hyperalgesia and allodynia. Alfentanil reduced these pain responses in a plasma-concentration-dependent manner, and reduction in hyperalgesia and allodynia correlated with reduction in acute pain. Amitriptyline alone had no effect and did not potentiate alfentanil. Alfentanil produced concentration-dependent nausea, an effect diminished by amitriptyline.

Discussion

These data correspond with previous studies in volunteers demonstrating reduction in hyperalgesia and allodynia after intradermal injection of capsaicin by systemically administered opioids, and they suggest that this reduction may be secondary to reduced nociceptive input by acute analgesia. These data do not support the use of acute systemic administration of amitriptyline for acute pain, hyperalgesia, and allodynia, although the roles of chronic treatment and spinal administration are being investigated.
Effects of Concentration and Volume of 2-Chloroprocaine on Epidural Anesthesia in Volunteers
Authors: Liu Spencer S. , Ware Paul D. , Rajendran Sundar
Published: November 2003

Background

Effect of local anesthetic concentration and volume on the spread and density of epidural anesthesia is unclear. This study was performed to delineate effects of a threefold difference in concentration and volume of 2-chloroprocaine on epidural anesthesia.

Methods

Twelve healthy volunteers underwent lumbar epidural anesthesia with 300 mg of 2-chloroprocaine as a 3% (10 ml) and a 1% (30 ml) solution in a randomized, double-blind, balanced, crossover fashion. Sensory block was assessed with pinprick, touch (calibrated plastic filament), cold, and electrical stimulation. Motor block was assessed at the quadriceps and gastrocnemius muscles with isometric force dynamometry. Differences between solutions were assessed with repeated measures analysis of variance followed by post hoc testing.

Results

The number of dermatomes blocked to pinprick, touch, and cold was significantly greater with the 1% concentration (2 dermatomes greater than the 3% concentration on average, P < 0.05). Similar intensity of sensory block to electrical stimulation developed at the hip and knee and was unaffected by concentration of 2-chloroprocaine. Similar intensity of motor block developed at the quadriceps with both concentrations.

Conclusions

Intensity of sensory and motor block from epidural anesthesia with 2-chloroprocaine appears to depend primarily on total milligram dose.
The Effect of Isoflurane, Halothane, Sevoflurane, and Thiopental/Nitrous Oxide on Respiratory System Resistance after Tracheal Intubation
Authors: Rooke G. Alec , Choi Jong-Ho , Bishop Michael J.
Published: November 2003

Background

After tracheal intubation, lung resistance and therefore respiratory system resistance (R[rs]) routinely increase, sometimes to the point of clinical bronchospasm. Volatile anesthetics generally have been considered to be effective bronchodilators, although there are few human data comparing the efficacy of available agents. This study compared the bronchodilating efficacy of four anesthetic maintenance regimens: 1.1 minimum alveolar concentration (MAC) end-tidal sevoflurane, isoflurane or halothane, and thiopental/nitrous oxide.

Methods

Sixty-six patients underwent tracheal intubation after administration of 2 microg/kg fentanyl, 5 mg/kg thiopental, and 1 mg/kg succinylcholine. Vecuronium or pancuronium (0.1 mg/kg) was then given to ensure paralysis during the rest of the study. Postintubation R(rs) was measured using the isovolume technique. Maintenance anesthesia was then randomized to thiopental 0.25 mg x kg(-1) x min(-1) plus 50% nitrous oxide, or 1.1 MAC end-tidal isoflurane, halothane, or sevoflurane. The R(rs) was measured after 5 and 10 min of maintenance anesthesia. Data were expressed as means +/- SD.

Results

Maintenance with thiopental/nitrous oxide failed to decrease R(rs), whereas all three volatile anesthetics significantly decreased R(rs) at 5 min with little further improvement at 10 min. Sevoflurane decreased R(rs) more than either halothane or isoflurane (P < 0.05; 58 +/- 14% of the postintubation R(rs) vs. 69 +/- 20% and 75 +/- 13%, respectively).

Conclusions

After tracheal intubation in persons without asthma, sevoflurane decreased R(rs) as much or more than isoflurane or halothane did during a 10-min exposure at 1.1 MAC.
The Cerebral Pharmacokinetics of Meperidine and Alfentanil in Conscious Sheep
Authors: Upton Richard N. , Ludbrook Guy L. , Gray Elke C. , Grant Clifford
Published: November 2003

Background

Different opioids have different delays (hysteresis) between their concentrations in blood and their cerebral effects. Possible mechanisms include differences in their rate of penetration into the brain and differences in their distribution volume in the brain. There have been few in vivo studies of the cerebral kinetics of opioids to differentiate these mechanisms.

Methods

The cerebral kinetics of meperidine and alfentanil were examined using conscious sheep that were fitted with long-term monitoring equipment to measure relative changes in cerebral blood flow and opioid concentration gradients across the brain through frequent sampling of arterial and sagittal sinus blood. The data were compared using hybrid physiologic modeling with membrane-limited (consistent with mechanism 1) and flow-limited (consistent with mechanism 2) models of cerebral kinetics.

Results

Alfentanil had a variable effect on relative cerebral blood flow, whereas meperidine induced a transient increase. The arteriovenous concentration gradients were small after alfentanil but large after meperidine. The flow-limited model gave acceptable descriptions of observed sagittal sinus concentrations for alfentanil and meperidine, whereas the membrane-limited model collapsed to a flow-limited model. The half-lives of equilibrium between blood and brain were 6.3 and 0.8 min for meperidine and alfentanil, respectively:

Conclusions

The rate of penetration of both opioids into the brain was rapid and not rate-limiting. Large differences in the cerebral distribution volume of meperidine and alfentanil accounted for the respective delays in their peak brain concentration relative to blood.
Synergistic Inhibition of Muscarinic Signaling by Ketamine Stereoisomers and the Preservative Benzethonium Chloride
Authors: Durieux Marcel E. , Nietgen Gregor W.
Published: November 2003

Background

Ketamine (Ketalar; Parke-Davis, Morris Plains, NJ) has been shown to inhibit muscarinic signaling with a median inhibitory concentration (IC50) of 5.7 microM. Whereas Ketalar is a racemic mixture, recent interest has focused on clinical use of the S(+) ketamine isomer, which is three times as potent an analgesic as the R(-) isomer yet seems to be associated with fewer psychoactive side effects. Therefore, the authors studied the effects of S(+) and R(-) ketamine and the preservative benzethonium chloride on muscarinic signaling.

Methods

Rat ml muscarinic acetylcholine receptors were expressed recombinantly in Xenopus laevis oocytes. Ca2(+)-activated Cl- currents in response to 10(-7) M acetyl-beta-methylcholine were determined by two-electrode voltage clamping in the presence of various concentrations of ketamine and benzethonium. Concentration-inhibition curves were constructed and used for algebraic and isobolographic analysis.

Results

The IC50. was 125 +/- 33 microM for S(+) ketamine, and 91 +/- 19 microM for R(-) ketamine. This difference was not statistically significant, indicating that muscarinic inhibition by ketamine is not stereoselective. The R(-)/S(+) mixture had an IC50 of 48 +/- 1 microM, and thus the stereoisomers interact synergistically. When appropriate concentrations of benzethonium were added, an IC50 of 15 +/- 2 microM resulted.

Conclusions

The muscarinic inhibitory action of ketamine isomers is not stereoselective. Because S(+) ketamine is a significantly more potent analgesic, it should have less muscarinic inhibitory action than R(-) ketamine when used in clinically equivalent doses. A significant fraction of the muscarinic inhibitory action of Ketalar is due to the preservative benzethonium. If reconstituted with a different preservative, Ketalar might be a less potent muscarinic antagonist.
Endobronchial Vasopressin Improves Survival during Cardiopulmonary Resuscitation in Pigs
Authors: Wenzel Volker , Lindner Karl H. , Prengel Andreas W. , Lurie Keith G. , Strohmenger Hans U.
Published: November 2003

Background

Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to be more effective than optimal doses of epinephrine. This study evaluated the effect of endobronchial vasopressin during CPR.

Methods

After 4 min of untreated ventricular fibrillation and 3 min of CPR, 21 pigs were randomized to be treated with 0.8 U/kg intravenous vasopressin (n = 7), 0.8 U/kg endobronchial vasopressin (n = 9), or an endobronchial placebo of normal saline (n = 5). Defibrillation was performed 5 min after drug administration to attempt return of spontaneous circulation.

Results

All animals in the intravenous and endobronchial vasopressin group were resuscitated successfully, but only two of five animals in the placebo group were. At 2 and 5 min after drug administration, coronary perfusion pressure in the intravenous and endobronchial vasopressin group was significantly higher than in the placebo group (50 +/- 10, 34 +/- 5 vs. 16 +/- 6 mmHg, respectively; and 35 +/- 10, 39 +/- 10 vs. 19 +/- 5 mmHg, respectively; P < 0.05).

Conclusions

Endobronchial vasopressin is absorbed during CPR, coronary perfusion pressure is increased significantly within a short period, and the chance of successful resuscitation is increased in this porcine model of CPR. Endobronchial vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.
The Effects of Heparinase 1 and Protamine on Platelet Reactivity
Authors: Ammar Tameshwar , Fisher Cherie F.
Published: November 2003

Background

Protamine is currently the most widely used drug for the reversal of heparin anticoagulation. Heparinase 1 (heparinase) is being evaluated as a possible alternative to protamine for the reversal of heparin anticoagulation. The authors evaluated the effects of equivalent doses of heparinase and protamine on platelet reactivity by measuring agonist-induced P-selectin expression.

Methods

After Institutional Review Board (IRB) approval, informed consent was obtained from 12 healthy volunteers and 8 patients undergoing surgery requiring cardiopulmonary bypass (CPB). Twenty-four ml of blood was obtained from each volunteer; 10 ml of blood was obtained from each patient before the CPB, and another 10 ml was obtained after CPB. Heparin was neutralized using heparinase or protamine. Platelet reactivity was assessed by measuring the expression of P-selectin after stimulation of platelets with increasing concentrations of a thrombin receptor agonist peptide (TRAP). Data were analyzed using analysis of variance. P < 0.05 was considered significant.

Results

For the healthy volunteers, the activated coagulation times (ACTs) of the heparinized samples returned to baseline values with heparinase (12.5 U/ml) or protamine (32.5 microg/ml). For the 8 patients, the ACTs returned to baseline with heparinase (20 U/ml) or protamine (50 microg/ml). The authors found no difference in the expression of P-selectin in samples neutralized with heparinase, but samples neutralized with protamine showed a significant decrease in the expression of P-selectin when compared with heparinized samples.

Conclusions

At dosages that reverse the anticoagulant effects of heparin, heparinase has minimal effects on platelets, whereas platelet reactivity was markedly inhibited by protamine.
Transmyocardial Laser Revascularization Induces Cerebral Microembolization
Authors: von Knobelsdorff Georg , Brauer Patrick , Tonner Peter H. , Hanel Frank , Naegele Herbert , Stubbe Hans-Martin , am Esch Jochen Schulte
Published: November 2003

Background

Transmyocardial laser revascularization may vaporize fluid in the left heart, allowing bubbles to form. This study aimed to determine whether the laser pulse resulted in cerebral emboli and to examine changes in middle cerebral artery flow velocity and jugular bulb oxygen saturation (SjO2) during transmyocardial laser revascularization.

Methods

Twelve patients (American Society of Anesthesiologists physical status III) were studied after the authors received institutional review board approval and the patients' informed consent. Monitored variables included mean arterial blood pressure (measured in millimeters of mercury), heart rate (measured as beats/min), and partial pressure of carbon dioxide (measured in millimeters of mercury). A 5-MHz transesophageal-sonography system was used to record intraventricular events after laser injection. Mean blood flow velocity (Vmean; measured in centimeters per second) was monitored in the middle cerebral artery using transcranial Doppler sonography, and SjO2 (expressed as a percentage) was measured using a fiberoptic thermodilution catheter placed in the right jugular bulb. Data were recorded before, during, and for 4 min after laser injection.

Results

After laser injection, intraventricular echogenic contrast was seen in transesophageal-sonography, and 2-4 s later high-intensity signals (microemboli) appeared in the transcranial Doppler sonography spectra. As long as mean arterial pressure remained stable during the observation period, Vmean and SjO2 did not change.

Conclusions

These data show that microemboli can be detected after laser injection in the middle cerebral artery, although they do not effect Vmean and SjO2. The results suggest that these microemboli do not induce a global oxygen imbalance.
Assessment of the Potency and Intrinsic Activity of Systemic versus Intrathecal Opioids in Rats
Authors: Abram Stephen E. , Mampilly George A. , Milosavljevic Douglas
Published: November 2003

Background

One measure of an opioid's efficacy is its ability to retain its analgesic effect as the intensity of a noxious stimulus is increased. A few studies have assessed the ability of either spinal or systemic opioids to produce analgesia using low- and high-intensity stimulation. There are little data available to show whether there are differences in efficacy between systemic and intrathecal opioid administration. The purpose of this study was to assess the relative efficacy of several clinically useful opioids systemically and spinally and to determine whether intrathecal administration resulted in greater efficacy than systemic administration.

Methods

Groups of rats were administered multiple doses of meperidine, morphine, hydromorphone, fentanyl, sufentanil, or buprenorphine either subcutaneously or intrathecally via implanted catheters. Noxious radiant heat was applied sequentially to each hindpaw, one at low intensity (adjusted to a mean withdrawal latency of 10 s) and one at high intensity (adjusted to a mean withdrawal latency of 5 s). Paw withdrawal latencies were recorded; dose-response curves for each intensity and each route of administration were graphically recorded, and ED50s were calculated. Ratios of high-to low-stimulus intensity ED50s were calculated for both routes of administration for each drug, and the ratios of subcutaneous-to-intrathecal ED50s for low-intensity stimulation were calculated to assess the relative systemic versus spinal potencies for each drug.

Results

The ratios of the high-to-low intensity ED50s were meperidine, 11.8, morphine, 6.1, hydromorphone, 2.6, fentanyl, 2.3, sufentanil, 1.8, and buprenorphine, 24.0. For intrathecal administration, there was uniformity of the high- to low-intensity ED50 ratios for the agonist drugs (meperidine, 2.1; morphine, 2.1; hydromorphone, 1.9; fentanyl, 1.8; sufentanil, 1.6). For morphine and hydromorphone, the systemic ED50 doses were several hundred times the intrathecal ED50s whereas the systemic-to-spinal ED50 ratios for the other drugs were 20 or less.

Conclusions

As intensity of noxious stimulation is increased, the more potent opioid agonists, administered systemically, produce antinociception with lesser increases in dose compared with lower potency drugs such as meperidine or morphine. When given spinally all opioid agonists tested, including morphine and meperidine, demonstrated good efficacy, as measured by their ability to provide antinociception for high versus low intensity stimulation.
Obstetric Anesthesia Work Force Survey, 1981 versus 1992
Authors: Hawkins Joy L. , Gibbs Charles P. , Orleans Miriam , Martin-Salvaj Gallice , Beaty Brenda
Published: November 2003

Background

In 1981, with support from the American Society of Anesthesiologists and the American College of Obstetricians and Gynecologists, anesthesia and obstetric providers were surveyed to identify the personnel and methods used to provide obstetric anesthesia in the United States. The survey was expanded and repeated in 1992 with support from the same organizations.

Methods

Comments and questions from the American Society of Anesthesiologists Committee on Obstetrical Anesthesia and the American College of Obstetricians and Gynecologists Committee on Obstetric Practice were added to the original survey instrument to include newer issues while allowing comparison with data from 1981. Using the American Hospital Association registry of hospitals, hospitals were differentiated by number of births per year (stratum I, > or = 1,500 births; stratum II, 500-1,499 births; stratum III, < 500 births) and by U.S. census region. A stratified random sample of hospitals was selected. Two copies of the survey were sent to the administrator of each hospital, one for the chief of obstetrics and one for the chief of anesthesiology.

Results

Compared with 1981 data, there was an overall reduction in the number of hospitals providing obstetric care (from 4,163 to 3,545), with the decrease occurring in the smallest units (56% of stratum III hospitals in 1981 compared with 45% in 1992). More women received some type of labor analgesia and there was a 100% increase in the use of epidural analgesia. However, regional analgesia was unavailable in 20% of the smallest hospitals. Spinal analgesia for labor was used in 4% of parturients. In 1981, obstetricians provided 30% of epidural analgesia for labor; they provided only 2% in 1992. Regional anesthesia was used for 78-85% (depending on strata) of patients undergoing cesarean section, resulting in a marked decrease in the use of general anesthesia. Anesthesia for cesarean section was provided by nurse anesthetists without the medical direction of an anesthesiologist in only 4% of stratum I hospitals but in 59% of stratum III hospitals. Anesthesia personnel provided neonatal resuscitation in 10% of cesarean deliveries compared with 23% in 1981.

Conclusions

Compared with 1981, analgesia is more often used by parturients during labor, and general anesthesia is used less often in patients having cesarean section deliveries. In the smallest hospitals, regional analgesia for labor is still unavailable to many parturients, and more than one half of anesthetics for cesarean section are provided by nurse anesthetists without medical direction by an anesthesiologist. Obstetricians are less likely to personally provide epidural analgesia for their patients. Anesthesia personnel are less involved in newborn resuscitation.
Volume Kinetics of Ringer Solution, Dextran 70, and Hypertonic Saline in Male Volunteers
Authors: Svensen Christer , Hahn Robert G.
Published: November 2003

Background

A knowledge of the distribution of different fluids given by intravenous infusion is basic to the understanding of the effects of fluid therapy. Therefore, a mathematical model was tested to analyze the volume kinetics of three types of fluids.

Methods

The authors infused 25 ml/kg of Ringer acetate solution, 5 ml/kg of 6% dextran 70 in 0.9% NaCl, and 3 ml/kg of 7.5% NaCl over 30 min in 8 male volunteers aged from 25 to 36 years (mean, 31 years) and measured the changes in total hemoglobin, serum albumin, and total blood water over time. The changes were expressed as fractioned dilution and then plotted against time. The curves were fitted to a one-volume and a two-volume model, which allowed an estimation of the size of the body fluid space expanded by the fluid (V) and the elimination rate constant (k(r) to be made.

Results

The changes in blood water concentration indicated a mean size of V of 5.9 1 (+/- 0.8, SEM) for Ringer's solution, 2.6 (+/- 0.3) 1 for dextran, and 1.2 (+/- 0.1) 1 for hypertonic saline. The corresponding values of k(r) were 94 (+/- 42), 12 (+/- 6), and 30 (+/- 4) ml/min, respectively. Blood hemoglobin indicated a degree of dilution similar to that indicated by blood water. Serum albumin indicated a more pronounced dilution, which resulted in a larger expandable volume and a greater mean square error for the curvefitting. The larger volume obtained for serum albumin can probably be explained by a loss of intravascular albumin into the tissues along with the infused fluid.

Conclusions

The distribution of intravenous fluids can be analyzed by a kinetic model adapted for fluid spaces, but slightly different results are obtained, depending on the marker used to indicate dilution of the primary fluid space. Analysis and simulation of plasma volume expansion by this model is a tool that can help the anesthetist to better plan fluid therapy.
Reduction by Fentanyl of the Cp50Values of Propofol and Hemodynamic Responses to Various Noxious Stimuli
Authors: Kazama Tomiei , Ikeda Kazuyuki , Morita Koji
Published: November 2003

Background

Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia.

Methods

Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation.

Results

The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp50loss of consciousness, 4.4 microg/ml (range, 3.8-5.0); Cp50tetanus, 9.3 microg/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 microg/ml (range, 8.9-10.8); Cp50skin incision, 10.0 microg/ml (range, 8.1-12.2); and Cp50intubation, 17.4 microg/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion.

Conclusions

The authors successfully defined the propofol concentration required for various stimuli. Tracheal intubation was the strongest stimulus. The absence of somatic reactions for propofol does not guarantee hemodynamic stability without fentanyl. Propofol with fentanyl was able to suppress motor and hemodynamic reactions to various noxious stimuli.
Dose Comparison of Remifentanil and Alfentanil for Loss of Consciousness
Authors: Jhaveri Rajiv , Joshi Pradip , Batenhorst Randall , Baughman Verna , Glass Peter
Published: November 2003

Background

This study evaluated the efficacy and safety of remifentanil, a potent mu agonist opioid with a rapid onset and offset of effect, as a sole induction agent for loss of consciousness (LOC) and compared it with alfentanil.

Methods

Remifentanil and alfentanil were administered intravenously over 2 min in ascending doses (remifentanil 2, 3, 4, 5, 6, 8, 10, 15, 20 microg/kg; alfentanil 40, 60, 80, 100, 120, 160, 200 microg/kg) to unpremedicated healthy patients. Patients were observed for rigidity and LOC for 30 s after the end of infusion. If patients had not lost consciousness, 2 mg x kg(-1) x min(-1) thiopental was administered until LOC was achieved. Arterial blood samples, obtained at specified time intervals, were analyzed for remifentanil and alfentanil whole-blood concentration. Blood pressure and heart rate were also recorded at preset time intervals.

Results

Neither drug could reliably produce LOC. With both drugs, there was a dose-dependent decrease in thiopental requirements and a dose-dependent increase in the incidence and severity of rigidity (P < 0.05). The median effective dose (ED50) for LOC with remifentanil was 12 microg/kg, and for alfentanil it was 176 mcrog/kg. The median effective concentration (EC50; whole-blood concentration) of remifentanil was 53.8 ng/ml and for alfentanil it was 1,012 ng/ml. Minimal hemodynamic changes were observed after either drug was given.

Conclusions

Remifentanil is 15 times more potent than alfentanil, based on the ED50 to achieve loss of response to a verbal command and 20 times more potent than alfentanil based on the EC50. Neither opioid is suitable as a sole induction agent.
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.