bluuebunny/crossref_metadata_2025 huggingface dataset:
A Physiologic Assessment of Intrathecal Amitriptyline in Sheep
Authors: Cerda Sergio E. , Tong Chuanyao , Deal Dwight D. , Eisenach James C.
Published: November 2003

Background

Intrathecal injection of amitriptyline enhances antinociception from intravenous morphine and reduces neuropathic pain behavior in animals. This study represents part of a preclinical assessment of intrathecal amitriptyline to determine its safety for use in humans.

Methods

Low thoracic intrathecal, femoral, and pulmonary arterial catheters were inserted in 18 adult ewes, followed 96 h later by intrathecal injection of saline or 5 mg amitriptyline and by determination of spinal cord blood flow, hemodynamic variables, behavioral changes, cerebrospinal fluid concentrations of catecholamines and amitriptyline, and spinal tissue concentrations of amitriptyline. In six other ewes, low thoracic intrathecal and femoral arterial catheters were inserted and blood pressure and heart rate were measured after intrathecal injection of saline or 0.25, 1, or 5 mg amitriptyline. Four other ewes received cervical intrathecal injection of 5 and 10 mg amitriptyline, and antinociception was determined.

Results

Thoracic intrathecal injection of amitriptyline produced dose-dependent sedation but did not significantly affect spinal cord blood flow or hemodynamic variables. Spinal cord tissue concentrations of amitriptyline were 100 times greater in tissue near the tip of the thoracic intrathecal catheter compared with cervical cord tissue. Cerebrospinal fluid concentrations of catecholamines did not significantly change after amitriptyline was administered. Cervical intrathecal injection of 5 mg amitriptyline produced mild antinociception, whereas 10 mg produced intense sedation and, in one sheep, seizures and death.

Conclusions

Although other preclinical toxicity studies are necessary before introducing intrathecal amitriptyline for use in humans, this study did not reveal dangerous changes in blood pressure or spinal cord blood flow from this agent.
Assessment of Low-flow Sevoflurane and Isoflurane Effects on Renal Function Using Sensitive Markers of Tubular Toxicity
Authors: Kharasch Evan D. , Frink Edward J. , Zager Richard , Bowdle T. Andrew , Artru Alan , Nogami Wallace M.
Published: November 2003

Background

Carbon dioxide absorbents degrade sevoflurane, particularly at low gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A). Compound A causes renal proximal tubular injury in rats but has had no effect on blood urea nitrogen (BUN) or creatinine concentrations in patients. This investigation compared the effects of low-flow sevoflurane and isoflurane on renal tubular function in surgical patients using conventional (BUN and creatinine) and finer indices of renal injury, specifically those biomarkers sensitive for compound A toxicity in rats (glucosuria, proteinuria, and enzymuria [N-acetyl-beta-D-glucosaminidase (NAG) and alpha-glutathione-S-transferase (alpha GST)]).

Methods

Consenting patients with normal preoperative renal function at two institutions were randomized to receive sevoflurane (n = 36) or isoflurane (n = 37) in oxygen and air. Total gas flow was 1 l/min, opioid doses were minimized, and barium hydroxide lime was used to maximize anesthetic degradation. Inspiratory and expiratory compound A concentrations were quantified every 30-60 min. Blood and urine were obtained before and 24-72 h after anesthesia for laboratory evaluation.

Results

Sevoflurane and isoflurane groups were similar with respect to age, weight, sex, American Society of Anesthesiologists status, anesthetic duration (3.7 or 3.9 h), and anesthetic exposure (3.6 or 3 minimum alveolar concentration [MAC]-hour). Maximum inspired compound A concentration (mean +/- standard deviation) was 27 +/- 13 ppm (range, 10-67 ppm). Areas under the inspired and expired compound A concentration versus time curves (AUC) were 79 +/- 54-ppm-h (range, 10-223 ppm-h) and 53 +/- 40 ppm-h (range, 6-159 ppm-h), respectively. There was no significant difference between anesthetic groups in postoperative serum creatinine or BUN, or urinary excretion of protein, glucose, NAG, proximal tubular alpha GST, or distal tubular pi GST. There was no significant correlation between compound A exposure (AUC) and protein, glucose, NAG, alpha GST, or pi GST excretion. Postoperative alanine and aspartate aminotransferase concentrations were not different between the anesthetic groups, and there were no significant correlations between compound A exposure and alanine or aspartate aminotransferase concentrations.

Conclusions

The renal tubular and hepatic effects of low-flow sevoflurane and isoflurane were similar as assessed using both conventional measures of hepatic and renal function and more sensitive biochemical markers of renal tubular cell necrosis. Moderate duration low-flow sevoflurane anesthesia, during which compound A formation occurs, appears to be as safe as low-flow isoflurane anesthesia.
Concentration-effect Relations for Intravenous Lidocaine Infusions in Human Volunteers
Authors: Wallace Mark S. , Laitin Steve , Licht Darren , Yaksh Tony L.
Published: November 2003

Background

Preclinical studies have emphasized that persistent small afferent input will induce a state of central facilitation that can be regulated by systemically administered lidocaine. The authors extended these preclinical studies to human volunteers by examining the concentration-dependent effects of intravenous lidocaine on acute sensory thresholds and facilitated processing induced by intradermal capsaicin.

Methods

Fifteen healthy persons received a lidocaine or a placebo infusion. A computer-controlled infusion pump targeted sequential stepwise increases in plasma lidocaine concentration steps of 1, 2, and 3 microg/ml. At each plasma concentration, neurosensory testing (thermal and von Frey hair test stimulation) were performed. After completing the tests at the 3 microg/ml plasma lidocaine level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair stimulation, stroking, and heat was assessed.

Results

The continuous infusion of lidocaine and placebo had no significant effect on any stimulus threshold. Although intravenous lidocaine resulted in a decrease in all secondary hyperalgesia responses, this was only significant for heat hyperalgesia. Intravenous lidocaine resulted in a significant decrease in the flare response induced by intradermal capsaicin.

Conclusions

These studies suggest that the facilitated state induced by persistent small afferent input human pain models may predict the activity of agents that affect components of nociceptive processing that are different from those associated with the pain state evoked by "acute" thermal or mechanical stimuli. Such insight may be valuable in the efficient development of novel analgesics for both neuropathic and post-tissue-injury pain states.
ORG 9487 Neuromuscular Block at the Adductor Pollicis and the Laryngeal Adductor Muscles in Humans
Authors: Debaene Bertrand , Lieutaud Thomas , Billard Valerie , Meistelman Claude
Published: November 2003

Background

ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a rapid onset of action. This study was designed to determine the neuromuscular blocking profile of ORG 9487 at the adductor muscles of the larynx and the adductor pollicis.

Methods

In 30 adults, anesthesia was induced with propofol (2-5 mg/kg) and fentanyl (2-3 microg/kg). After train-of-four stimulation, the block of the laryngeal adductor muscles was evaluated by measuring the pressure changes in the cuff of the tracheal tube placed between the vocal cords, and the force of the contraction of the adductor pollicis was measured with a force transducer. Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses of 0.75, 1.5 or 2 mg/kg (n = 10 in each group).

Results

Time to peak effect was significantly shorter at the vocal cords than at the adductor pollicis muscle (P < 0.001). Onset time at the vocal cords was 62 +/- 16 s, 62 +/- 13 s, and 52 +/- 14 s (mean +/- SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not significant). Onset time at the adductor pollicis muscle was 126 +/- 33 s, 96 +/- 20 s, and 82 +/- 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P < 0.001). Maximum block was significantly less intense at the vocal cords than at the adductor pollicis muscle (69 +/- 15% vs. 94 +/- 4% after 0.75 mg/kg; 86 +/- 7% vs. 97 +/- 4% after 1.5 mg/kg; and 91 +/- 5% vs. 99 +/- 1% after 2 mg/kg). After 1.5 mg/kg duration to 25%, recovery was 3.7 +/- 2.2 min versus 10.2 +/- 2.5 min at the vocal cords and the adductor pollicis muscle, respectively, and 75% recovery occurred at 9.7 +/- 3.7 min at the vocal cords and at 18.3 +/- 5.2 min at the adductor pollicis muscle.

Conclusions

ORG 9487 has a rapid onset of action at the laryngeal adductor and the adductor pollicis muscles. Onset and duration of action are faster at the vocal cords than at the adductor pollicis muscle. However, the maximum block obtained at the laryngeal muscles was less than at the adductor pollicis, regardless of the dose of ORG 9487.
Effects of Intracoronary Fentanyl on Left Ventricular Mechanoenergetics in the Excised Cross-circulated Canine Heart
Authors: Kohno Kunihisa , Takaki Miyako , Ishioka Kazunari , Nakayama Yasunori , Suzuki Shunsuke , Araki Junichi , Namba Taketoshi , Suga Hiroyuki
Published: November 2003

Background

It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts.

Methods

This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross-circulated canine hearts. The authors used the framework of the E(max) (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate E(max), PVA, and VO2. They first obtained the VO2-PVA relationship for varied LV volumes at control E(max). The authors then obtained the VO2-PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2-PVA relationship for varied LV volumes at the final dose of fentanyl.

Results

Fentanyl at any concentrations did not significantly change E(max), PVA, and VO2 from the control. The linear end-systolic pressure-volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2-PVA relationship remained unchanged by fentanyl.

Conclusions

These results indicate that intracoronary fentanyl produces virtually no effects on LV mechanoenergetics for a wide range of its blood concentration.
Increase of Glutamate Uptake in Astrocytes
Authors: Miyazaki Hirofumi , Nakamura Yoichi , Arai Tatsuru , Kataoka Kiyoshi
Published: November 2003

Background

Glutamate is the most ubiquitous excitatory neurotransmitter in the vertebrate central nervous system. Astrocytes play an important role in terminating glutamatergic neurotransmission by removing released glutamate from the synaptic cleft. The authors examined the effects of several anesthetics on the glutamate uptake activity of astrocytes.

Methods

Cultured astrocytes from hippocampi of rat embryos were incubated with solution containing [3H]glutamate, which was pre-equilibrated with 0-4% halothane at 37 degrees C. The uptake activity was evaluated as the amount of radioactivity per cell of protein.

Results

When the reaction solution was equilibrated with 4% halothane, glutamate uptake increased to about 165% of the control. The effect of halothane was dose-dependent, and a significant augmentation (30-50%) of glutamate uptake was observed at a range in clinical use concentrations (1-2%). On the other hand, the uptake of gamma-aminobutyric acid, an inhibitory transmitter, was hardly affected by 1-4% halothane. The effect of halothane on glutamate uptake was also examined in neuron-rich culture, and similar augmentation was observed, although the extent was less than that in astrocyte culture. Biochemical subcellular fractions (i.e., glial plasmalemmal vesicles and synaptosomes) were also examined, however, only slight (not significant) increase was detected in the glutamate uptake activity. Other volatile anesthetics, such as enflurane, isoflurane, and sevoflurane, also enhanced glutamate uptake, whereas the intravenous anesthetics ketamine and pentobarbital showed no effect on glutamate uptake.

Conclusions

The increase of glutamate uptake by astrocytes in the presence of volatile anesthetics potentially attenuates excitatory synaptic transmission in the entire central nervous system, a finding that may explain in part the action of volatile anesthetics.
Intrathecal α2-Adrenergic Agonists Stimulate Acetylcholine and Norepinephrine Release from the Spinal Cord Dorsal Horn in Sheep
Authors: Klimscha W. , Tong C. , Eisenach J. C.
Published: November 2003

Background

Intrathecal injection of clonidine and dexmedetomidine produce behavioral analgesia by an alpha 2-adrenergic mechanism. Functional and anatomic studies suggest that this analgesia is mediated by cholinergic activation. This hypothesis was directly tested by measuring extracellular acetylcholine concentrations in spinal cord interstitial fluid by means of microdialysis after intrathecal injection of these alpha 2-adrenergic agonists in sheep.

Methods

Twelve sheep with chronically implanted thoracic intrathecal catheters were anesthetized with halothane. Multiple 200-micron-diameter dialysis fibers were inserted surgically at a mid-thoracic level through the dorsal horn and perfused with artificial cerebrospinal fluid. After baseline sampling, either clonidine (100 micrograms), dexmedetomidine (100 micrograms), or saline were injected intrathecally. Microdialysis samples were analyzed by high-pressure liquid chromatography for acetylcholine and norepinephrine.

Results

Both alpha 2-adrenergic agonists increased acetylcholine in microdialysate, whereas intrathecal saline had no effect. Analysis of the raw data showed that all groups differed significantly, with greater levels of acetylcholine following administration of dexmedetomidine than clonidine or saline. Unexpectedly, intrathecal clonidine also increased microdialysate norepinephrine levels.

Conclusions

These data are consistent with previous experiments measuring acetylcholine concentrations in cerebrospinal fluid and support analgesia from alpha 2-adrenergic agonists mediated in part by cholinergic activation. In addition, the increase in norepinephrine concentrations after intrathecal administration of clonidine suggest stimulation of norepinephrine release by this agent.
Actions of Phenylephrine, Isoproterenol, and Epinephrine Halothane on Endocardial Conduction and Activation in Canine Left Ventricular Papillary Muscles
Authors: Vodanovic Sanja , Turner Lawrence A. , Hoffmann Raymond G. , Kampine John P. , Bosnjak Zeljko J.
Published: November 2003

Background

Myocardial sensitization by halothane to the arrhythmogenic effects of epinephrine involves synergistic actions mediated by alpha 1- and beta-adrenoceptors. Halothane potentiates a transient a1-adrenoceptor-mediated negative dromotropic effect of epinephrine on Purkinje fibers. This study examines how halothane alters the actions of alpha 1- and beta-agonists and epinephrine on endocardial conduction.

Methods

Superfused canine papillary muscles were mapped to locate a Purkinje-ventricular muscle junction (PVJ), and bipolar electrodes were placed to measure Purkinje and endocardial conduction velocity and PVJ conduction time during stimulation of the Purkinje layer. The effects of exposure to 5 microM phenylephrine, 1 microM isoproterenol, or 5 microM epinephrine on conduction were determined in the absence and presence of 0.4 mM halothane in three groups of 10 preparations.

Results

Isoproterenol slightly increased Purkinje conduction velocity and markedly improved conduction at the PVJ and in the endocardium similarly in the presence or absence of halothane. Phenylephrine depressed Purkinje velocity (-12%) only in the presence of halothane and did not slow conduction at the PVJ or in the myocardium. Epinephrine transiently depressed Purkinje velocity, more so with (-22%) than without (-12%) halothane (P < or = 0.01), and simultaneously facilitated conduction at the PVJ and in the myocardium.

Conclusions

The prodysrhythmic actions of epinephrine with halothane may involve disparate effects on conduction, including speeding on conduction at the PVJ and in the myocardium, similar to that produced by isoproterenol, accompanied by simultaneous but transient alpha 1-mediated depression of conduction in the Purkinje system.
Isoflurane Mimics Ischemic Preconditioning via Activation of KATPChannels
Authors: Kersten Judy R. , Schmeling Todd J. , Pagel Paul S. , Gross Garrett J. , Warltier David C.
Published: November 2003

Background

The authors tested the hypothesis that isoflurane directly preconditions myocardium against infarction via activation of K(ATP) channels and that the protection afforded by isoflurane is associated with an acute memory phase similar to that of ischemic preconditioning.

Methods

Barbiturate-anesthetized dogs (n = 71) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size was assessed by triphenyltetrazolium chloride staining. All dogs were subjected to a single prolonged (60 min) left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Ischemic preconditioning was produced by four 5-min LAD occlusions interspersed with 5-min periods of reperfusion before the prolonged LAD occlusion and reperfusion. The actions of isoflurane to decrease infarct size were examined in dogs receiving 1 minimum alveolar concentration (MAC) isoflurane that was discontinued 5 min before prolonged LAD occlusion. The interaction between isoflurane and ischemic preconditioning on infarct size was evaluated in dogs receiving isoflurane before and during preconditioning LAD occlusions and reperfusions. To test whether the cardioprotection produced by isoflurane can mimic the acute memory of ischemic preconditioning, isoflurane was discontinued 30 min before prolonged LAD occlusion and reperfusion. The mechanism of isoflurane-induced cardioprotection was evaluated in two final groups of dogs pretreated with glyburide in the presence or absence of isoflurane.

Results

Myocardial infarct size was 25.3 +/- 2.9% of the area at risk during control conditions. Isoflurane and ischemic preconditioning produced significant (P < 0.05) and equivalent reductions in infarct size (ischemic preconditioning alone, 9.6 +/- 2.0; isoflurane alone, 11.8 +/- 2.7; isoflurane and ischemic preconditioning, 5.1 +/- 1.9%). Isoflurane-induced reduction of infarct size also persisted 30 min after discontinuation of the anesthetic (13.9 +/- 1.5%), independent of hemodynamic effects during LAD occlusion. Glyburide alone had no effect on infarct size (28.3 +/- 3.9%), but it abolished the protective effects of isoflurane (27.1 +/- 4.6%).

Conclusions

Isoflurane directly preconditions myocardium against infarction via activation of K(ATP) channels in the absence of hemodynamic effects and exhibits acute memory of preconditioning in vivo.
Serious Complications Related to Regional Anesthesia
Authors: Auroy Yves , Narchi Patrick , Messiah Antoine , Litt Lawrence , Rouvier Bernard , Samii Kamran
Published: November 2003

Background

Serious complications related to regional anesthesia have previously been described primarily in case reports and retrospective surveys. The authors prospectively evaluated a multicenter series of regional anesthetics, using preplanned criteria to measure the incidence and characteristics of associated serious complications.

Methods

Requests were sent to 4,927 French anesthesiologists in advance of a subsequent 5-month study period. Participating anesthesiologists were asked for detailed reports of serious complications occurring during or after regional anesthetics performed by them during the study interval. Details regarding each complication then were obtained via a second questionnaire.

Results

The number of responding anesthesiolgists was 736. The number of regional anesthetics performed was 103,730, corresponding to 40,640 spinal anesthetics, 30,413 epidural anesthetics, 21,278 peripheral nerve blocks, and 11,229 intravenous regional anesthetics. Reports of 98 severe complications were received, with follow-up information being obtained for 97. In 89 cases, complications were attributed fully or partially to regional anesthesia. Thirty-two cardiac arrests, seven of which were fatal, occurred during the study. Of these, 26 occurred during spinal anesthesia, with 6 being fatal, 3 occurred during epidural anesthesia, and 3 more occurred during peripheral blocks. The higher incidence of cardiac arrest during spinal anesthesia (6.4 +/- 1.2 per 10,000 patients) compared with all other regional anesthesia (1.0 +/- 0.4 per 10,000 patients) was statistically significant (P < 0.05). Of 34 neurologic complications (radiculopathy, cauda equina syndrome, paraplegia), 21 were associated either with paresthesia during puncture (n = 19) or with pain during injection (n = 2), suggesting nerve trauma or intraneural injection. Twelve patients who had neurologic complications after spinal anesthetics had no paresthesia during needle placement and no pain on injection. Of these 12 patients (7 with radiculopathy and 5 with cauda equina syndrome), 9 received intrathecal hyperbaric lidocaine, 5%. The incidence of neurologic injury was significantly greater after spinal anesthesia (6 +/- 1 per 10,000 cases; P < 0.05) than after each of the other types of regional procedures (1.6 +/- 0.5 per 10,000 cases for the weighted average). Seizures attributed to elevated serum levels of local anesthetics occurred in 23 patients, but none suffered a cardiac arrest.

Conclusions

(1) The incidence of cardiac arrest and neurologic injury related to regional anesthesia were very low, but both were more than three SDs greater after spinal anesthesia than after other regional procedures. (2) Two thirds of the patients with neurologic deficits had either a paresthesia during needle placement or pain on injection. (3) Seventy-five percent of the neurologic deficits after nontraumatic spinal anesthesia occurred in patients who had received hyperbaric lidocaine, 5%.
Cesarean Delivery
Authors: Sharma Shiv K. , Sidawi Elaine J. , Ramin Susan M. , Lucas Michael J. , Leveno Kenneth J. , Cunningham Gary F.
Published: November 2003

Background

Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries. However, only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery. The authors' primary purpose in this randomized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative: patient-controlled intravenous analgesia.

Methods

Seven hundred fifteen women of mixed parity in spontaneous labor at full term were randomly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia. Epidural analgesia was maintained with a continuous epidural infusion of 0.125% bupivacaine with 2 microg/ml fentanyl. Patient-controlled analgesia was maintained with 10-15 mg meperidine given every 10 min as needed using a patient-controlled pump. Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman randomized in the study.

Results

A total of 358 women were randomized to receive epidural analgesia, and 243 (68%) of these women complied with the epidural analgesia protocol. Similarly, 357 women were randomized to receive patient-controlled intravenous meperidine analgesia, and 259 (73%) of these women complied with the patient-controlled intravenous analgesia protocol. Only five women who were randomized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief. There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original randomization (epidural analgesia, 4% [95% CI: 1.9-6.2%] compared with patient-controlled intravenous analgesia, 5% [95% CI: 2.6-7.2%]). Similar results were observed for the analysis of the protocol-compliant groups (epidural analgesia, 5% [95% CI: 2.6-8.5%] compared with patient-controlled intravenous analgesia, 6% [95% CI: 3-8.9%]). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia.

Conclusions

Epidural analgesia was not associated with increased numbers of cesarean delivery when compared with a suitable alternative method of analgesia.
Monitoring Gastric Mucosal Carbon Dioxide Pressure Using Gas Tonometry
Authors: Creteur Jacques , De Backer Daniel , Vincent Jean-Louis
Published: November 2003

Background

Saline gastric tonometry of carbon dioxide has been proposed as a means to assess the adequacy of splanchnic perfusion. However, this technique has several disadvantages, including the long time interval needed for gases to reach equilibrium in saline milieu. Thus the authors evaluated a system that uses a gas-filled instead of a saline-filled gastric balloon.

Methods

In vitro, we simultaneously placed two tonometry catheters in an equilibration water bath maintained at a predetermined and constant pressure of carbon dioxide (P(CO2)). The first catheter's balloon was filled with air and the second with saline. The performance of gas tonometry was tested by comparing the P(CO2) measurements of the bath obtained via gas tonometry (PgCO2) to the P(CO2) measurements of direct bath samples (PbathCO2). These results were also compared with the P(CO2) measurements obtained simultaneously by saline tonometry (PsCO2). The response time of gas versus saline tonometry was also studied. In vivo, the performance of gas tonometry was tested comparing the measurements of gastric intramucosal P(CO2) obtained by gas tonometry (PgCO2) at different equilibration times with those obtained by saline tonometry (PsCO2) using an equilibration time of 30 min. Two nasogastric tonometry catheters were placed simultaneously in seven stable patients in the intensive care unit. The first balloon was filled with air and the second with saline.

Results

In vitro, there was a close correlation between PgCO2 and PbathCO2, for each level of PbathCO2, and for each different gas equilibration time. For an equilibration time of 10 min at a PbathCO2 level of approximately 40 mmHg, the bias of the gas device defined as the mean of the differences between PbathCO2 and PgCO2 and its precision defined as the standard deviation of the bias, were -0.3 mmHg and 0.7 mmHg, respectively. Using the same definitions, the bias and precision of saline tonometry were 11.2 mmHg and 1.4 mmHg, respectively. If the equilibration time-dependent correction factor provided by the catheter manufacturer for saline tonometry was applied, the bias and precision were -6.9 mmHg and 2.9 mmHg, respectively. In vivo, using an equilibration time of 10 min for gas and 30 min for saline tonometry, there was a close correlation between the two techniques (r2 = 0.986). A Bland and Altman analysis revealed a bias (+/- 2 SD) of 0.1 +/- 6.8 mmHg. The correlation between the two methods was not improved if we prolonged the equilibration time of the gas tonometer.

Conclusions

Gas tonometry is comparable to saline tonometry for measuring gastric intramucosal P(CO2). Because gas tonometry is easier to automate, it may offer advantages over saline tonometry.
Blood Flow Velocity of Middle Cerebral Artery during Prolonged Anesthesia with Halothane, Isoflurane, and Sevoflurane in Humans
Authors: Kuroda Yasuhiro , Murakami Mari , Tsuruta Junko , Murakawa Toshisuke , Sakabe Takefumi
Published: November 2003

Background

It is not clear whether the increase of cerebral blood flow (CBF) produced by volatile anesthetics is maintained during prolonged anesthesia. In a previous study, the authors found that CBF equivalent, an index of flow-metabolism relationship, was stable over 3 h, suggesting no decay over time in CBF for 3 h during volatile anesthesia in humans. However, it may be possible that CBF changes in a parallel fashion to functional metabolic changes. In this study, to estimate the response of CBF to three volatile anesthetics, the authors used transcranial Doppler (TCD) ultrasonography to measure time-averaged mean velocity in the middle cerebral artery (Vmca).

Methods

Twenty-four surgical patients were randomly assigned to three groups to receive halothane, isoflurane, or sevoflurane (eight patients, each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5, 1.0, and 1.5 MAC before surgery and then at 1.5 MAC during surgery, which lasted more than 3 h. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 70 mmHg, using phenylephrine infusion, if necessary. TCD recordings of the Vmca were performed continuously.

Results

Vmca at 0.5 MAC of halothane, isoflurane, and sevoflurane was 49 +/- 19, 57 +/- 8, and 48 +/- 13 cm/s, respectively. Halothane significantly (P < 0.01) increased Vmca in a dose-dependent manner (0.5, 1.0, 1.5 MAC), whereas isoflurane and sevoflurane produced no significant dose-related changes. At 1.5 MAC for 3 h, Vmca changed significantly (P < 0.05) for the time trends, but it did not exhibit decay over time with all drugs. During burst suppression, observed electroencephalographically (EEG) on patients during isoflurane and sevoflurane anesthesia, the onset of a burst increased Vmca (approximately 5-30 cm/s), which was maintained for the duration of the burst.

Conclusions

The results indicate that there was no decay in Vmca over time during prolonged (3 h) inhalation of volatile anesthetics at 1.5 MAC in humans. The fluctuation of Vmca during burst suppression on EEG at 1.5 MAC indicates that the flow-metabolism coupling occurred.
Prevention of Methacholine-induced Changes in Respiratory Mechanics in Piglets
Authors: Habre Walid , Wildhaber Johannes H. , Sly Peter D.
Published: November 2003

Background

Sevoflurane is a new volatile anesthetic agent that may be a useful alternative to halothane for anesthesia in children. However, there is insufficient information about its effects on respiratory mechanics, particularly in the presence of constrictor stimuli.

Methods

Eighteen piglets had anesthesia induced and maintained with either pentobarbital (control: n = 8), 1 minimum alveolar concentration (MAC) sevoflurane (sevo: n = 5), or 1 MAC halothane (halo: n = 5). Pressure, flow, and volume were measured at the airway opening and used to calculate lung compliance (C(L)) and resistance (R(L)). Resistance was partitioned into airway (Raw) and parenchymal (Vti) components using alveolar pressure. Methacholine was infused intravenously in a dose sufficient (15 microg x kg(-1) x h(-1)) to approximately double R(L).

Results

The increase in R(L) seen in the control group was almost entirely due to an increase in Vti. Sevoflurane and halothane prevented the increase in R(L) and Vti (both P < 0.02) and the decrease in C(L) (both P < 0.02).

Conclusions

Sevoflurane and halothane can prevent methacholine-induced changes in lung function.
Pregnancy Does Not Increase Susceptibility to Bupivacaine in Spinal Root Axons
Authors: Dietz Friederike B. , Jaffe Richard A.
Published: November 2003

Background

The underlying mechanism of enhanced antinociceptive effects and increased susceptibility to local anesthetics during pregnancy is not known. Mechanical, hormonal, biochemical, and neural changes have been suggested. The authors measured the susceptibility of individual spinal root axons to bupivacaine during late pregnancy in rats and compared them with similar measurements in nonpregnant rats.

Methods

Lumbar dorsal and ventral roots were excised from anesthetized pregnant and nonpregnant rats. Single-fiber dissection and recording techniques were used to isolate activity in individual axons. Supramaximal constant voltage stimuli were delivered to the distal end of the root. During in vitro perfusion, each root was exposed to increasing concentrations of bupivacaine, and the minimum blocking concentration (Cm) and the concentration that increased conduction latency by 50% (EC50) were measured.

Results

Myelinated and unmyelinated dorsal and ventral root axons of pregnant rats appeared to be less sensitive to steady-state conduction block and to the latency-increasing effects of bupivacaine than were equivalent axons from nonpregnant rats. Although when comparing specific axon types, only the difference in C-fibers was significant (Cm = 29.8 microM for pregnant and Cm = 22.1 microM for nonpregnant rats, P < 0.05; EC50 = 19.9 microM and 13.6 microM, respectively).

Conclusions

In contrast to clinical expectations, the susceptibility to bupivacaine conduction block in individual dorsal and ventral root axons during late pregnancy in rats was not greater in pregnant animals. Pregnancy-related changes in diffusion barriers and activation of endogenous analgesic systems without changes in the electrophysiologic properties of spinal root axons are suggested as possible explanations for the discrepancy between clinical and experimental observations.
Neutrophil Elastase Inhibitor, ONO-5046, Modulates Acid-induced Lung and Systemic Injury in Rabbits
Authors: Kaneko Kazuhiro , Kudoh Ichidai , Hattori Satoshi , Yamada Hiroshi , Ohara Maria , Wiener-Kronish Jeanine , Okumura Fukuichiro
Published: November 2003

Background

Acid instillation leads to direct lung and to secondary systemic organ injury, probably via activated macrophages and neutrophils. This study investigated the effects of neutrophil elastase on organ injury after unilateral lung acid instillation by administrating a specific neutrophil elastase inhibitor, ONO-5046, before acid instillation.

Methods

Three groups of anesthetized rabbits (n = 12 in each group) underwent tracheostomies, and instillations were made into their right lower lobe airspaces with either phosphate buffered saline (pH, 7.4; volume, 1.2 ml/kg; n = 12) or HCl (pH, 1.25; volume, 1.2 ml/kg; n = 24). In half of the acid-instilled rabbits, ONO-5046, 10 mg/kg, was given intravenously 15 min before the HCl instillation, and then 10 mg x kg(-1) x h(-1) of the drug was continuously infused throughout the experiment. The other groups of animals received the vehicle intravenously. Anesthesia and mechanical ventilation was continued for 8 h, whereas arterial blood gases were sampled intermittently. Eight hours after saline or acid instillation, the animals were killed, and their lungs, heart, kidneys, liver, and small intestines were harvested. Wet-to-dry weight ratios (W/ D) and myeloperoxidase (MPO) assays of these organs were done, and elastase assays on the bronchoalveolar lavage fluids (BALF) obtained from each lung also were performed.

Results

Pretreatment with ONO-5046 attenuated the physiologic changes seen in the vehicle-treated animals. Significant decreases in W/D of the noninstilled lungs and of the small intestine and normalization of the oxygenation of the experimental animals occurred. The ONO-5046 pretreatment did not affect the neutrophil sequestration in the lungs or in the other organs as determined by neutrophil counts in BALF and by the MPO assays.

Conclusions

A neutrophil elastase inhibitor, ONO-5046, administered immediately before acid instillation attenuated the physiologic changes seen in the vehicle-treated animals. The drug blocked neutrophil elastase but did not block neutrophil sequestration in the lungs, although the drug improved measurements of lung injury.
Nitrous Oxide Impairs Electrophysiologic Recovery after Severe Hypoxia in Rat Hippocampal Slices
Authors: Amorim Pedro , Chambers Geoffrey , Cottrell James , Kass Ira S.
Published: November 2003

Background

Research has suggested that nitrous oxide may be harmful to ischemic neurons; however, the evidence for this is equivocal. The authors used rat hippocampal slices to examine the effects of nitrous oxide on neuronal hypoxic damage.

Methods

The evoked population spike (PS) was recorded from hippocampal CA1 pyramidal cells before, during, and after hypoxia. Control groups received nitrogen concentrations equal to nitrous oxide throughout the experiments. Biochemical measurements were made from dissected CA1 regions under experimental conditions that matched the electrophysiology studies.

Results

Recovery of the PS after hypoxia was 18 +/- 7% in slices treated with 50% nitrous oxide before and during 3.5 min of hypoxia; this compares with 41 +/- 9% (P < 0.05) in nitrogen-treated slices. Slices treated with nitrous oxide (95%) only during hypoxia (6 min) also demonstrated significantly less recovery of the PS than did slices treated with nitrogen. There was no significant difference in recovery if nitrous oxide was discontinued after the hypoxic period. Adenosine triphosphate concentrations after 3.5 min of hypoxia in slices treated with nitrous oxide decreased to the same extent as in nitrogen-treated slices (47% vs. 50%). Calcium influx increased during 10 min of hypoxia in untreated slices, but nitrous oxide did not significantly increase calcium influx during hypoxia. The sodium concentrations increased and potassium concentrations decreased during hypoxia; nitrous oxide did not significantly alter these changes.

Conclusions

Nitrous oxide impaired electrophysiologic recovery of hippocampal slices after severe hypoxia. Nitrous oxide did not cause significant changes in the biochemical parameters examined.
Effects of Intracoronary Fentanyl on Left Ventricular Mechanoenergetics in the Excised Cross-circulated Canine Heart (Revised Publication)
Authors: Kohno Kunihisa , Takaki Miyako , Ishioka Kazunari , Nakayama Yasunori , Suzuki Shunsuke , Araki Junichi , Namba Taketoshi , Suga Hiroyuki
Published: November 2003

Background

It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts.

Methods

This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross-circulated canine hearts. The authors used the framework of the Emax (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate Emax, PVA, and VO2. They first obtained the VO2-PVA relationship for varied LV volumes at control Emax. The authors then obtained the VO2-PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2-PVA relationship for varied LV volumes at the final dose of fentanyl.

Results

Fentanyl at any concentrations did not significantly change Emax, PVA, and VO2 from the control. The linear end-systolic pressure-volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2-PVA relationship remained unchanged by fentanyl.

Conclusions

These results indicate that intracoronary fentanyl produces virtually no effects on LV mechanoenergetics for a wide range of its blood concentration.
Comparative Hemodynamic Depression of Sevoflurane versus Halothane in Infants
Authors: Wodey Eric , Pladys Patrick , Copin Catherine , Lucas Marie Madeleine , Chaumont Andre , Carre Philippe , Lelong Bernard , Azzis Olivier , Ecoffey Claude
Published: November 2003

Background

The cardiovascular side effects of volatile anesthetics are one of the chief causes of postoperative complications in children, and infants seem to be at the greatest risk for this. This study compared cardiovascular changes at equipotent concentrations of sevoflurane and halothane in infants.

Methods

Thirty infants classified as American Society of Anesthesiologists physical status I or II who required elective surgery were randomized to receive either halothane or sevoflurane for inhalation induction. Cardiovascular and echocardiographic data were recorded in both groups at baseline and at end-tidal concentrations of 1 and 1.5 minimum alveolar concentration (MAC).

Results

Sevoflurane did not alter heart rate or cardiac index at all concentrations compared with awake values. Sevoflurane significantly decreased blood pressure and systemic vascular resistance compared with awake values at all concentrations. Shortening fraction and rate-corrected velocity of circumferential fiber shortening decreased at 1.5 but not at 1 MAC. Myocardial contractility assessed by stress-velocity index and stress-shortening index decreased significantly at all concentrations, but did not fall into the abnormal range at any concentration. Halothane caused a greater decrease in heart rate, shortening fraction, stress-shortening index, velocity of circumferential fiber shortening, stress-velocity index, and cardiac index at all concentrations than did sevoflurane.

Conclusion

Sevoflurane causes a lesser decrease in cardiac output than does halothane in infants.
Predictive Factors in Global and Anesthesia Satisfaction in Ambulatory Surgical Patients
Authors: Tong Doris , Chung Frances , Wong David
Published: November 2003

Background

Patient satisfaction is one of the variables that affect the outcome of health care and the use of health-care services. As more procedures are performed on an ambulatory basis, the role of the anesthesiologist becomes more important. To improve the delivery of care, the predictors of dissatisfaction with the entire process (global dissatisfaction) of ambulatory surgery and with anesthesia itself must be identified. The authors conducted a hypothesis-generating study to identify predictors; specifically, they hypothesized that satisfaction with anesthesia was a predictor of global satisfaction with ambulatory surgery and that 24-h postoperative symptoms were a predictor of satisfaction with anesthesia.

Methods

The authors prospectively studied 5,228 consecutive patients having surgery in the ambulatory setting during a 1-yr period. Preoperative, intraoperative, and postoperative variables were gathered and patient satisfaction was assessed using a postoperative telephone questionnaire administered 24 h after operation in 2,730 respondents. Significant univariate variables and clinically important variables were entered into multiple logistic regression models. Qualitative data on dissatisfaction were obtained by asking patients' reasons for dissatisfaction.

Results

Sixty-eight of the 2,730 respondents (2.5%) had global dissatisfaction with ambulatory surgery. Nine of these patients were dissatisfied with anesthesia. Dissatisfaction with anesthesia was associated with a 12-fold increase in global dissatisfaction (P = 0.0001). Thirty-one of the 2,730 respondents (1.1%) were dissatisfied with anesthesia. An increasing number of symptoms occurring 24 h after operation was associated with an exp(0.28 x N)-fold increase in dissatisfaction with anesthesia for N number of symptoms (P = 0.0001). Qualitative data showed that the most common reason for global dissatisfaction with ambulatory surgery was personal preference for inpatient care (26%), whereas intraoperative and postoperative adverse outcomes were the major causes of dissatisfaction with anesthesia (88%).

Conclusions

Dissatisfaction with anesthesia is a predictor of global dissatisfaction with ambulatory surgery. An increasing number of symptoms 24 h after operation is a predictor of dissatisfaction with anesthesia. The rate of global dissatisfaction and anesthesia dissatisfaction is very low. The predictors from this model need to be validated by a second data set from either this or another center. Given the low rate of dissatisfaction, a focused study testing specific interventions to improve patient satisfaction would be difficult.
Development of a Measure of Patient Satisfaction with Monitored Anesthesia Care
Authors: Dexter Franklin , Aker John , Wright Will A.
Published: November 2003

Background

The authors describe development of the Iowa Satisfaction with Anesthesia Scale (ISAS) for monitored anesthesia care (MAC). Patients complete the self-administered written questionnaire before discharge from the hospital. The authors designed the ISAS to measure satisfaction with MAC itself, not the perioperative experience. Patients respond to eleven statements (e.g., "I felt pain") by placing a mark along a six-choice vertical response column (e.g., "Disagree moderately") below each statement. The mean of their responses to each of the 11 statements gives a single number, which is a quantitative measure of a patient's satisfaction with their MAC.

Methods

Adult, English-speaking patients completed the questionnaires following admission to a phase II postanesthesia care unit after MAC.

Results

Response rate for MAC was 92% (86 of 94 patients). Patients completed the questionnaire in 4.6 +/- 2.3 min. Internal consistency, Cronbach's alpha, equaled 0.80. Patients' scores were positively correlated with those predicted by their anesthesia provider (r2 = 0.23) and with responses to the question "I was satisfied with my anesthetic care" (Kendall's tau = +0.41). Scores on initial and repeat questionnaires were positively correlated (r2 = 0.74). Scores on initial questionnaires and those completed within 4.4 +/- 1.7 days postoperatively were positively correlated (r2 = 0.76).

Conclusions

The authors have developed and tested an internally consistent, reliable, and valid measure of patient satisfaction with MAC.