bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic and Metabolic Manifestations of Acute Endotoxin Infusion in Pigs with and without the Malignant Hyperthermia Mutation
Authors: Musley Shailesh Kumar V. , Beebe David S. , Komanduri Vijaya , Iaizzo Paul A. , Belani Kumar G.
Published: November 2003

Background

The hypermetabolic state induced by acute endotoxemia and malignant hyperthermia (MH) may be indistinguishable. The aims of this study were (1) to investigate the differences between MH and sepsis, (2) to determine whether acute endotoxemia can trigger MH, and (3) to establish the effects of dantrolene in these two disorders.

Methods

Three groups of swine were studied. All pigs were invasively monitored and initially anesthetized with nontriggering agents. A placebo MH-susceptible group (n = 5) received normal saline whereas the endotoxin groups (MH-susceptible, n = 6; MH-negative, n = 4) received intravenous endotoxin (250 microg/kg total) during 2.5 h. Halothane (1.5%) and succinylcholine (2-4 mg/kg) were then administered, followed by two doses of dantrolene (4 mg/kg total).

Results

Endotoxin infusion resulted in pulmonary hypertension and systemic hypotension in pigs with and without the MH mutation, but did not trigger MH. Halothane and succinylcholine triggered MH, evidenced by a markedly higher oxygen consumption in the MH-susceptible pigs that received endotoxin (325+/-196 ml/min) and those that did not (374+/-110 ml/min) compared to the MH-negative pigs (69+/-15 ml/min, P<0.0009), as well as muscular rigidity in the susceptible animals. Dantrolene reversed these changes. Three of the six MH-susceptible pigs that received endotoxin died; two died soon after triggering and one after dantrolene administration. In contrast, none of the MH-negative pigs or the MH-susceptible pigs that did not receive endotoxin died (0 of 9 vs. 3 of 6, P = 0.044).

Conclusion

Endotoxemia does not trigger MH, but may worsen outcome if it occurs.
Is Combined Spinal–Epidural Analgesia Associated with More Rapid Cervical Dilation in Nulliparous Patients When Compared with Conventional Epidural Analgesia?
Authors: Tsen Lawrence C. , Thue Brad , Datta Sanjay , Segal Scott
Published: November 2003

Background

The combined spinal-epidural technique provides rapid onset of labor analgesia and, anecdotally, is associated with labors of shorter duration. Epidural analgesia, by contrast, has been suggested to prolong labor modestly. It is unclear, however, whether more rapid cervical dilation in patients who receive combined spinal-epidural analgesia is a physiologic effect of the technique or an artifact of patient selection. The authors hypothesized that anesthetic technique may influence the rate of cervical dilation, and we compared the effects of combined spinalepidural with those of epidural analgesia on the rate of cervical dilation.

Methods

One hundred healthy nulliparous parturients in spontaneous labor with singleton, vertex, full-term fetuses were enrolled in a double-blinded manner when their cervical dilation was less than 5 cm. The patients were randomly assigned to receive analgesia via a standardized combined spinal-epidural (n = 50) or epidural (n = 50) technique. Data were collected on cervical dilation, pain, sensory level, and motor blockade.

Results

When regional analgesia was induced in comparable groups at a mean of 3 cm cervical dilation, the mean initial cervical dilation rates were significantly faster in the combined spinal-epidural group (mean values, 2.1 +/- 2.1 cm/h vs. 1 +/- 1 cm/h; P = 0.0008). Five parturients in the combined spinal-epidural group had a very rapid (> 5 cm/h) rate of mean initial cervical dilation, compared with none of the women in the epidural group. Overall mean cervical dilation rates in patients who achieved full cervical dilation were 2.3 +/- 2.6 cm/h and 1.3 +/- 0.71 cm/h (P = 0.0154) in the combined spinal-epidural and epidural groups, respectively.

Conclusions

In healthy nulliparous parturients in early labor, combined spinal-epidural analgesia is associated with more rapid cervical dilation compared with epidural analgesia. Further study is needed to elicit the cause and overall effect of this difference.
Pharmacokinetics and Pharmacodynamics of Vecuronium in Rats with Systemic Inflammatory Response Syndrome
Authors: Blobner Manfred , Kochs Eberhard , Fink Heidrun , Mayer Barbara , Veihelmann Andreas , Brill Thomas , Stadler Josef
Published: November 2003

Background

Insufficient detoxification caused by nitric oxide-related inhibition of cytochrome P450 may be important for metabolism of numerous drugs, including vecuronium. The present study investigated the pharmacodynamics and pharmacokinetics of vecuronium in rats with inflammatory liver dysfunction.

Methods

Male Sprague-Dawley rats (n = 56) were randomly allocated into two groups: In the sepsis group, liver inflammation was established by injection of 56 mg/kg heat-killed Corynebacterium parvum; control rats received the solvent. At day 4, groups were subdivided according to treatment with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (250 mg/kg) or placebo. The aminopyrine breath test was performed to assess cytochrome P450 activity. Rats were anesthetized with propofol and mechanically ventilated. Duration of action of vecuronium (1.2 mg/kg) was measured by evoked mechanomyography (stimulation of the sciatic nerve, contraction of the gastrocnemius muscle). In seven rats of each subgroup a 50% neuromuscular blockade was established by a continuous vecuronium infusion. Vecuronium plasma levels were measured and plasma clearance of vecuronium was calculated. Nitric oxide synthesis was assessed by measuring nitrite/nitrate serum levels.

Results

In sepsis/placebo rats, vecuronium-induced neuromuscular blockade was prolonged (144% of contro/placebo), vecuronium plasma levels at 50% neuromuscular blockade were increased (122% of control/placebo), and plasma clearance was decreased (68% of control/placebo). N(G)-monomethyl-L-arginine therapy in rats with sepsis improved cytochrome P450 activity and plasma clearance of vecuronium, shortened duration of action of vecuronium, but did not alter the elevated vecuronium plasma levels.

Conclusions

A systemic inflammatory response syndrome with liver dysfunction results in decreased sensitivity to and a decreased elimination of vecuronium. Modulation of nitric oxide synthesis may be a strategy that can be used in the future to improve xenobiotic metabolism in sepsis.
Quantitative and Qualitative Effects of Isoflurane on Movement Occurring after Noxious Stimulation
Authors: Antognini Joseph F. , Wang Xiao Wei , Carstens E.
Published: November 2003

Background

Anesthetic potency is assessed by determination of the anesthetic concentration that prevents gross, purposeful movement in response to noxious stimulation. It is unclear whether anesthetics cause a progressive decrease in the number and force of limb movements evoked by noxious stimulation, or a step decrease (consistent with an all-or-none effect at the site of action). The authors hypothesized that isoflurane and halothane would progressively depress the movement response.

Methods

Isoflurane minimum alveolar concentration (MAC) was determined in rats (N = 14) using a clamp applied to a hind paw. Lateral head movements and flexions of the forelimbs and hindlimbs were measured with force transducers. Isoflurane was adjusted to 0.6, 0.9, 1.1, and 1.4 MAC, the noxious stimulus applied, and the force and number of limb and head movements determined. Force and movement determinations were made in seven additional halothane-anesthetized rats.

Results

Isoflurane MAC was 1.3 +/- 0.1%. In general, if movement occurred after application of the noxious clamp, the head and all limbs were involved. At 0.6 MAC, the median number of extremity and head movements was 3.5 (10th-90th percentile, 2.0-11.4) with force generated per movement (force/movement) = 6.4 (2.0-13.2) N-s. Movement number decreased to 2.1 (0.25-4.2) at 0.9 MAC (P < 0.05), but force/movement was unchanged at 4.5 (0.4-15.1) N-s (Newton-second). At 1.1 MAC, movement number and force/movement decreased to 0.2 (0.0-1.5) and 0.1 (0.0-3.2) N-s, respectively (P < 0.005). No significant movement occurred at 1.4 MAC. The halothane-anesthetized rats had similar findings, although at 0.6 MAC they generated more movements (10.5 [5.2-19.8]) than the rats receiving isoflurane (P < 0.05).

Conclusions

The results indicate that increasing anesthetic concentration from 0.6 to 0.9 MAC had little effect on the motor system controlling the force of limb movements, and the neural system generating repeated limb movements was depressed, consistent with a differential anesthetic effect at separate sites.
Inhibitory Effects of Propofol on Acetylcholine-induced, Endothelium-dependent Relaxation and Prostacyclin Synthesis in Rabbit Mesenteric Resistance Arteries
Authors: Yamashita Akiko , Kajikuri Junko , Ohashi Masuo , Kanmura Yuichi , Itoh Takeo
Published: November 2003

Background

Propofol (2,6-diisopropylphenol) modulates endothelium-dependent relaxation in some arterial preparations. The effect of propofol on endothelium-dependent, prostacyclin-mediated responses in mesenteric resistance arteries has not yet been clarified.

Methods

The effect of propofol was examined on acetylcholine-induced membrane potential changes in the presence of N(G)-nitro-L-arginine (L-NOARG) in endothelium-intact rabbit mesenteric resistance arteries in vitro. The effects of propofol were also examined on the endothelium-dependent relaxation and prostacyclin synthesis that was induced by acetylcholine in the presence of L-NOARG and nicardipine. The effect of propofol on the relaxation induced by a prostacyclin analogue was examined in strips treated with L-NOARG and diclofenac.

Results

Acetylcholine produced an initial and a slow membrane hyperpolarization. Propofol, 10 microM, and diclofenac each inhibited the acetylcholine-induced slow hyperpolarization, but not the initial hyperpolarization. Acetylcholine produced an endothelium-dependent relaxation that was significantly inhibited by propofol, 10 microM, and diclofenac. Propofol, 10 microM, greatly inhibited the acetylcholine-induced synthesis of prostacyclin, as did diclofenac. Propofol, 10 microM, had no effect on the relaxation induced by a prostacyclin analog.

Conclusions

In rabbit mesenteric resistance arteries, propofol inhibits the synthesis of prostacyclin and thus attenuates acetylcholine-induced, endothelium-dependent responses. Our results may help to explain why some actions seen with propofol in some preparations (e.g., vasoconstriction) are not seen after the endothelium is removed.
Supplemental Oxygen Reduces the Incidence of Postoperative Nausea and Vomiting
Authors: Greif Robert , Laciny Sonja , Rapf Brigitta , Hickle Randy S. , Sessler Daniel I.
Published: November 2003

Background

Despite new anesthetic drugs and antiemetics, particularly 5-hydroxytryptamines, the incidence of postoperative nausea or vomiting remains between 20% and 70%. The authors tested the hypothesis that supplemental perioperative oxygen administration reduces the incidence of postoperative nausea or vomiting.

Methods

Patients undergoing colon resection were anesthetized with fentanyl and isoflurane. During and for 2 h after surgery they were randomly assigned to (1) 30% oxygen, balance nitrogen (n = 119); or (2) 80% oxygen, balance nitrogen (n = 112). The incidence of nausea or vomiting during the first 24 postoperative hours was evaluated by nurses blinded to group assignment and oxygen concentration. Data were analyzed with unpaired t or Mann-Whitney U tests. Results are presented as means +/- SD; P < 0.05 was considered significant.

Results

Factors known to influence nausea and vomiting were comparable in the two groups. Perioperative oxygen saturation was well within normal limits in each treatment group; saturations the first postoperative morning were comparable in each group. Supplemental oxygen reduced the incidence of postoperative nausea or vomiting from 30% in the patients given 30% oxygen to 17% in those given 80% oxygen (P = 0.027).

Conclusions

Supplemental oxygen reduced the incidence of postoperative nausea or vomiting nearly twofold after colorectal surgery. The mechanism by which oxygen administration reduces the incidence of these postoperative sequelae remains unknown but may be related to subtle intestinal ischemia. Because oxygen is inexpensive and essentially risk-free, supplemental oxygen appears to be an effective method of reducing postoperative nausea and vomiting.
Intramuscular Rapacuronium in Infants and Children
Authors: Reynolds Lynne M. , Infosino Andrew , Brown Ronald , Hsu James , Fisher Dennis M.
Published: November 2003

Background

Intravenous rapacuronium's rapid onset and short duration suggest that intramuscular rapacuronium might facilitate tracheal intubation without prolonged paralysis. Accordingly, the authors injected rapacuronium into the deltoid muscle to determine the optimal dose and time for intubation in pediatric patients.

Methods

Unpremedicated patients (aged, 2 months to 3 yr) were studied. Part I: Spontaneous minute ventilation (V(E)) and twitch tension were measured during N2O/halothane anesthesia. Rapacuronium (2.2-5.5 mg/kg, given intramuscularly, n = 23), succinylcholine (4 mg/kg, given intramuscularly, n = 12), or vecuronium (0.1 mg/kg, given intravenously, n = 15) was given. Time to 50% depression of V(E) and 10% recovery of twitch were measured. Dose for each patient was changed 10-20% according to the previous patient's response. Part II: In 22 patients anesthetized with 0.82-1.0% halothane, the optimal rapacuronium dose determined in part I (infants, 2.8 mg/kg; children, 4.8 mg/kg) was given intramuscularly. Laryngoscopy was scored. Time to laryngoscopy was increased or decreased 0.5 min according to the previous patient's response.

Results

Part I: Rapacuronium typically depressed ventilation in < or = 2 min with 10% twitch recovery in 20-60 min. With succinylcholine, median time to ventilatory depression was 1.3 and 1.1 min for infants and children, respectively; for vecuronium, 0.7 and 0.6 min. Part I: Intubating conditions were good-excellent at 3.0 and 2.5 min in infants and children, respectively; time to 10% twitch recovery (mean +/- SD) was 31 +/- 14 and 36 +/- 14 min in the two groups.

Conclusions

This pilot study indicates that deltoid injection of rapacuronium, 2.8 mg/kg in infants and 4.8 mg/kg in children, permits tracheal intubation within 2.5-3.0 min, despite a light plane of anesthesia. Duration of action is intermediate.
Intrathecal Neostigmine and Sufentanil for Early Labor Analgesia
Authors: Nelson Kenneth E. , D'Angelo Robert , Foss Michael L. , Meister Greg C. , Hood David D. , Eisenach James C.
Published: November 2003

Background

Recent efforts to improve the combined spinal epidural (CSE) technique have focused on adding opioids to other classes of analgesics. In this study, the authors used intrathecal neostigmine in combination with intrathecal sufentanil to investigate the usefulness of neostigmine for reducing side effects and prolonging the duration of sufentanil.

Methods

One hundred six healthy pregnant women in labor were enrolled in this study, which was divided into four phases. In all phases, patients received a CSE anesthetic while in the lateral position. In phase I, three groups of six women each received intrathecal neostigmine, 5, 10, or 20 microg, in an open-label, dose-escalating safety assessment. In phase II, 24 women received intrathecal sufentanil alone to establish an ED50 (dose that produces > 60 min of labor analgesia in 50% of patients). In phase III, an ED50 was established for sufentanil combined with a fixed dose of neostigmine (10 microg). In phase IV, 40 women received either twice the ED50 of sufentanil alone or twice the ED50 of sufentanil plus neostigmine, 10 microg.

Results

Neostigmine alone had no adverse effects on maternal vital signs, fetal heart rate, or Apgar scores. Neostigmine, 20 microg, produced analgesia in one patient and severe nausea and vomiting in another. The ED50 for intrathecal sufentanil alone was 4.1 +/- 0.31 microg, and the ED50 for intrathecal sufentanil combined with neostigmine, 10 microg, was 3.0 +/- 0.28 microg. The duration of analgesia and side effects from double these ED50s (sufentanil, 9 microg, or sufentanil, 6 microg, plus neostigmine, 10 microg) were similar between groups.

Conclusions

The 10-microg intrathecal neostigmine dose alone produced no analgesia or side effects, but reduced the ED50 of intrathecal sufentanil by approximately 25%. Additionally, doses approximately double these ED50s each produced a similar duration of analgesia and side effects, indicating intrathecal neostigmine shifts the dose-response curve for intrathecal sufentanil to the left.
Amsorb
Authors: Murray James M. , Renfrew Craig W. , Bedi Amit , McCrystal Conor B. , Jones David S. , Fee Howard J. P.
Published: November 2003

Background

This article describes a carbon dioxide absorbent for use in anesthesia. The absorbent consists of calcium hydroxide with a compatible humectant, namely, calcium chloride. The absorbent mixture does not contain sodium or potassium hydroxide but includes two setting agents (calcium sulphate and polyvinylpyrrolidine) to improve hardness and porosity.

Methods

The resultant mixture was formulated and subjected to standardized tests for hardness, porosity, and carbon dioxide absorption. Additionally, the new absorbent was exposed in vitro to sevoflurane, desflurane, isoflurane, and enflurane to determine whether these anesthetics were degraded to either compound A or carbon monoxide. The performance data and inertness of the absorbent were compared with two currently available brands of soda lime: Intersorb (Intersurgical Ltd., Berkshire, United Kingdom) and Dragersorb (Drager, Lubeck, Germany).

Results

The new carbon dioxide absorbent conformed to United States Pharmacopeia specifications in terms of carbon dioxide absorption, granule hardness, and porosity. When the new material was exposed to sevoflurane (2%) in oxygen at a flow rate of 1 l/min, concentrations of compound A did not increase above those found in the parent drug (1.3-3.3 ppm). In the same experiment, mean +/-SD concentrations of compound A (32.5 +/- 4.5 ppm) were observed when both traditional brands of soda lime were used. After dehydration of the traditional soda limes, immediate exposure to desflurane (60%), enflurane (2%), and isoflurane (2%) produced concentrations of carbon monoxide of 600.0 +/- 10.0 ppm, 580.0 +/- 9.8 ppm, and 620.0 +/-10.1 ppm, respectively. In contrast, concentrations of carbon monoxide were negligible (1-3 ppm) when the anhydrous new absorbent was exposed to the same anesthetics.

Conclusions

The new material is an effective carbon dioxide absorbent and is chemically unreactive with sevoflurane, enflurane, isoflurane, and desflurane.
Human Neuronal Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes Predict Efficacy of Halogenated Compounds That Disobey the Meyer-Overton Rule
Authors: Cardoso Rita A. , Yamakura Tomohiro , Brozowski Susan J. , Chavez-Noriega Laura E. , Harris Adron R.
Published: November 2003

Background

According to the Meyer-Overton rule, anesthetic potency of a substance can be predicted by its lipid solubility, but a group of halogenated volatile compounds predicted to induce anesthesia does not obey this rule. Thus, these compounds are useful tools for studies of molecular targets of anesthetics. Human neuronal nicotinic acetylcholine receptor (hnAChR) subunits have been recently cloned, which allowed the authors to assess whether these receptors could differentiate among volatile anesthetic and nonimmobilizer compounds. This study provides the first data regarding anesthetic sensitivity of hnAChRs.

Methods

alpha2beta4, alpha3beta4, and alphaabeta2 hnAChRs were expressed in Xenopus oocytes, and effects of volatile anesthetics isoflurane and F3 (1-chioro-1,2,2-triflurocyclobutane, 1A) and nonimmobilizers F6 (1,2-dichlorohexafluorocyclobutane, 2N) and F8 (2,3-dichlorooctafluorobutane) on the peak acetylcholine-gated currents were studied using the two-electrode voltage-clamp technique.

Results

Isoflurane and F3 inhibited all the hnAChRs tested in a concentration-dependent manner. Isoflurane at a concentration corresponding to 1 minimum alveolar concentration (MAC) inhibited 83, 69, and 71% of ACh-induced currents in alpha2beta4, alpha3beta4, and alpha4beta2 hnAChRs, respectively, and 1 MAC of F3 inhibited 64, 44, and 61% of currents gated in those receptors. F6 (8-34 microM) did not cause any changes in currents gated by any of the receptors tested. F8 (4-18 microM) did not alter the currents gated in either alpha3beta4 or alpha4beta2 receptors, but caused a small potentiation of alpha2beta4 hnAChRs without a concentration-response relation.

Conclusion

The in vivo potency and effectiveness of volatile anesthetic and nonimmobilizer compounds were consistent with their actions on hnAChRs expressed in a recombinant expression system, suggesting a potential participation of these receptors in the mechanisms of anesthesia.
Forecasting Surgical Groups’ Total Hours of Elective Cases for Allocation of Block Time
Authors: Dexter Franklin , Macario Alex , Qian Fang , Traub Rodney D.
Published: November 2003

Background

Allocation of the correct amount of operating room (OR) "block time" can provide surgeons with access to sufficient OR time to complete their elective cases while optimally matching staffing with the elective case workload (to maximize labor productivity). To evaluate how to predict accurately total hours of elective cases performed by a surgical group using data from surgical services information systems, the authors addressed the following questions: (1) How many previous 4-week periods of data should be used to minimize error in forecasting a surgical group's total hours of elective cases? (2) Using the number of 4-week periods from question #1, can we detect trends or correlations between successive periods that could be used to improve forecasting accuracy? (3) How can results from questions #1 and #2 be used to calculate an upper prediction bound (upper limit) for the total hours of elective cases that will be completed in a future period? Prediction bounds can be used to budget staffing accurately.

Methods

Time series analysis was performed on total hours of elective cases over 39 consecutive 4-week periods from 17 surgical groups.

Results

The average of 12 consecutive periods' total hours of elective cases had an appropriate error profile. The observations within each series of 12 consecutive 4-week periods followed a normal distribution, with each observation of total hours of elective cases not correlated with the subsequent observation.

Conclusions

The average of the most recent 12 4-week periods can be used to predict surgical groups' future use of block time.
French Survey of Anesthesia in 1996
Authors: Clergue François , Auroy Yves , Péquignot Françoise , Jougla Eric , Lienhart André , Laxenaire Marie-Claire
Published: November 2003

Background

To identify the growth in the number of anesthetic procedures since 1980 and the changes in the practice of anesthesia, the present survey was designed to collect and analyze the anesthetic activity performed in France in 1996, from a representative sample collected in all French hospitals and clinics.

Methods

This study, initiated by the French Society of Anesthesia and Intensive Care, collected information that included the characteristics of patients (age, sex, American Society of Anesthesiologists status), the techniques of anesthesia, and the nature of the procedure for which anesthesia was required. All French private, public, and military hospitals were asked to participate in the survey. In each hospital in the country, all anesthetic procedures were documented and collected during 3 consecutive days, chosen at random during a 12-month period, to obtain a representative sample of the annual activity. All data were analyzed at the INSERM (National Institute of Health and MEDICAL RESEARCH: At the conclusion of the study, 5% of hospitals were randomly assigned to be audited to check for missing data and errors. The rate of anesthetic activity was calculated as the ratio between the annual number of anesthetic procedures and the number of the general population in the same age group.

Results

The participation rate of hospitals was 98%. The analysis of the 62,415 collected questionnaires allowed extrapolation of the anesthetic activity to 7,937,000 anesthetic procedures (95% confidence interval, +/- 387,000) performed in France in 1996. Thus, the annual rate of anesthetic procedures was 13.5 per 100 population, varying between 5.4 per 100 in girls aged 5-14 yr and 30.2 per 100 in men aged 75-84 yr. Surgery was involved in 71% of anesthesia cases. Regional anesthesia alone was performed in 20% of all surgical cases and was combined with general anesthesia in 3% of additional cases. Anesthesia for obstetric procedures represented 9% of all cases. Seventy-six percent of all anesthetic procedures started between 12:00 A.M. and 7:00 A.M. were related to obstetric activities.

Conclusion

In comparison with a previous study, the present survey shows that the number of anesthetic procedures has increased by 120% since 1980, and the rate of anesthetic procedures increased from 6.6 to 13.5 per 100 population, the major changes being observed in patients aged > or = 75 yr and in those with an American Society of Anesthesiologists physical status of 3. In the same time period, the number of regional anesthetic procedures increased 14-fold. In obstetrics, the practice of epidural analgesia extended from 1.5% to 51% of all deliveries of the country.
Selective iNOS Inhibition Attenuates Acetylcholine- and Bradykinin-induced Vasoconstriction in Lipopolysaccharide-exposed Rat Lungs
Authors: Fischer Lars G. , Horstman Damian J. , Hahnenkamp Klaus , Kechner Nancy E. , Rich George F.
Published: November 2003

Background

Nonselective nitric oxide synthase (NOS) inhibition has detrimental effects in sepsis because of inhibition of the physiologically important endothelial NOS (eNOS). The authors hypothesized that selective inducible NOS (iNOS) inhibition would maintain eNOS vasodilation but prevent acetylcholine- and bradykinin-mediated vasoconstriction caused by lipopolysaccharide-induced endothelial dysfunction.

Methods

Rats were administered intraperitoneal lipopolysaccharide (15 mg/kg) with and without the selective iNOS inhibitors L-N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg), dexamethasone (1 mg/kg), or the nonselective NOS inhibitor Nomega-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Six hours later, the lungs were isolated and pulmonary vasoreactivity was assessed with hypoxic vasoconstrictions (3% O2), acetylcholine (1 microg), Biochemical Engineering, and bradykinin (3 microg). In additional lipopolysaccharide experiments, L-NIL (10 microM) or 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 100 microM), a selective muscarinic M3 antagonist, was added into the perfusate.

Results

Exhaled nitric oxide was higher in the lipopolysaccharide group (37.7+/-17.8 ppb) compared with the control group (0.4+/-0.7 ppb). L-NIL and dexamethasone decreased exhaled nitric oxide in lipopolysaccharide rats by 83 and 79%, respectively, whereas L-NAME had no effect. In control lungs, L-NAME significantly decreased acetylcholine- and bradykinin-induced vasodilation by 75% and increased hypoxic vasoconstrictions, whereas L-NIL and dexamethasone had no effect. In lipopolysaccharide lungs, acetylcholine and bradykinin both transiently increased the pulmonary artery pressure by 8.4+/-2.0 mmHg and 35.3+/-11.7 mmHg, respectively, immediately after vasodilation. L-NIL and dexamethasone both attenuated this vasoconstriction by 70%, whereas L-NAME did not. The acetylcholine vasoconstriction was dose-dependent (0.01-1.0 microg), unaffected by L-NIL added to the perfusate, and abolished by 4-DAMP.

Conclusions

In isolated perfused lungs, acetylcholine and bradykinin caused vasoconstriction in lipopolysaccharide-treated rats. This vasoconstriction was attenuated by administration of the iNOS inhibitor L-NIL but not with L-NAME. Furthermore, L-NIL administered with lipopolysaccharide preserved endothelium nitric oxide-dependent vasodilation, whereas L-NAME did not.
First-pass Lung Uptake and Pulmonary Clearance of Propofol
Authors: Kuipers Jette A. , Boer Fred , Olieman Wim , Burm Anton G. L. , Bovill James G.
Published: November 2003

Background

The principal site for elimination of propofol is the liver. The clearance of propofol exceeds hepatic blood flow; therefore, extrahepatic clearance is thought to contribute to its elimination. This study examined the pulmonary kinetics of propofol using part of an indocyanine green (ICG) recirculatory model.

Methods

Ten sheep, immobilized in a hammock, received injections of propofol (4 mg/kg) and ICG (25 mg) via two semipermanent catheters in the right internal jugular vein. Arterial blood samples were obtained from the carotid artery. The ICG injection was given for measurement of intravascular recirculatory parameters and determination of differences in propofol and ICG concentration-time profiles. No other medication was given during the experiment, and the sheep were not intubated. The arterial concentration-time curves of ICG were analyzed with a recirculatory model. The pulmonary uptake and elimination of propofol was analyzed with the central part of that model extended with a pulmonary tissue compartment allowing elimination from that compartment.

Results

During the experiment, cardiac output was 3.90+/-0.72 l/min (mean +/- SD). The blood volume in heart and lungs, measured with ICG, was 0.66+/-0.07 l. A pulmonary tissue compartment of 0.47+/-0.16 l was found for propofol. The pulmonary first-pass elimination of propofol was 1.14+/-0.23 l/min. Thirty percent of the dose was eliminated during the first pass through the lungs.

Conclusions

Recirculatory modeling of ICG allows modeling of the first-pass pulmonary kinetics of propofol concurrently. Propofol undergoes extensive uptake and first-pass elimination in the lungs.
Interaction of Intravenous Anesthetics with Human Neuronal Potassium Currents in Relation to Clinical Concentrations
Authors: Friederich Patrick , Urban Bernd W.
Published: November 2003

Background

Neuronal voltage-dependent potassium (K) currents are crucial for various cellular functions, such as the integration of temporal information in the central nervous system. Data for the effects of intravenous anesthetics on human neuronal K currents are limited. It was the authors' aim to evaluate the concentration-related effects of three opioids (fentanyl, alfentanil, sufentanil) and seven nonopioids (thiopental, pentobarbital, methohexital, propofol, ketamine, midazolam, droperidol) used in clinical anesthesia on neuronal voltage-dependent K currents of human origin.

Method

K currents were measured in SH-SY5Y cells using the whole cell patch-clamp technique. Currents were elicited by step depolarization from a holding potential of -80 to -50 mV through +90 mV, and their steady state amplitudes were determined.

Results

All drugs inhibited the K currents in a concentration-dependent and reversible manner. Because time dependence of inhibition differed among the drugs, effects were measured after 54-64 ms of the test pulse. The IC50 values (concentration of half-maximal inhibition) for current suppression ranged from 7 microM for sufentanil to 2 mM for pentobarbital. Suppression of the K currents by the opioids occurred at 10-fold lower IC50 values (concentration of half-maximal inhibition) than that by the barbiturates. As estimated from the concentration-response curves, K-current suppression at clinical concentrations would be less than 0.1% for the opioids and approximately 3% for the other drugs.

Conclusions

Effects of intravenous anesthetics on voltage-dependent K currents occur at clinical concentrations. The IC50 values for current inhibition of the nonopioid anesthetics correlated with these concentrations (r = 0.95). The results suggest that anesthetic drug action on voltage-dependent K currents may contribute to clinical effects or side effects of intravenous anesthetics.
Hemodilution during Venous Gas Embolization Improves Gas Exchange, without Altering V̇A/Q̇ or Pulmonary Blood Flow Distributions
Authors: Deem Steven , McKinney Steven , Polissar Nayak L. , Hedges Richard G. , Swenson Erik R.
Published: November 2003

Background

Isovolemic anemia results in improved gas exchange in rabbits with normal lungs but in relatively poorer gas exchange in rabbits with whole-lung atelectasis. In the current study, the authors characterized the effects of hemodilution on gas exchange in a distinct model of diffuse lung injury: venous gas embolization.

Methods

Twelve anesthetized rabbits were mechanically ventilated at a fixed rate and volume. Gas embolization was induced by continuous infusion of nitrogen via an internal jugular venous catheter. Serial hemodilution was performed in six rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; six rabbits were followed as controls over time. Measurements included hemodynamic parameters and blood gases, ventilation-perfusion (V(A)/Q) distribution (multiple inert gas elimination technique), pulmonary blood flow distribution (fluorescent microspheres), and expired nitric oxide (NO; chemoluminescence).

Results

Venous gas embolization resulted in a decrease in partial pressure of arterial oxygen (PaO2) and an increase in partial pressure of arterial carbon dioxide (PaCO2), with markedly abnormal overall V(A)/Q distribution and a predominance of high V(A)/Q areas. Pulmonary blood flow distribution was markedly left-skewed, with low-flow areas predominating. Hematocrit decreased from 30+/-1% to 11+/-1% (mean +/- SE) with hemodilution. The alveolar-arterial PO2 (A-aPO2) difference decreased from 375+/-61 mmHg at 30% hematocrit to 218+/-12.8 mmHg at 15% hematocrit, but increased again (301+/-33 mmHg) at 11% hematocrit. In contrast, the A-aPO2 difference increased over time in the control group (P < 0.05 between groups over time). Changes in PaO2 in both groups could be explained in large part by variations in intrapulmonary shunt and mixed venous oxygen saturation (SvO2); however, the improvement in gas exchange with hemodilution was not fully explained by significant changes in V(A)/Q or pulmonary blood flow distributions, as quantitated by the coefficient of variation (CV), fractal dimension, and spatial correlation of blood flow. Expired NO increased with with gas embolization but did not change significantly with time or hemodilution.

Conclusions

Isovolemic hemodilution results in improved oxygen exchange in rabbits with lung injury induced by gas embolization. The mechanism for this improvement is not clear.
Nursing Workload Associated with Adverse Events in the Postanesthesia Care Unit
Authors: Cohen Marsha M. , O'Brien-Pallas Linda L. , Copplestone Christine , Wall Ronald , Porter Joan , Rose Keith D.
Published: November 2003

Background

The authors used a nursing task inventory system to assess nursing resources for patients with and without adverse postoperative events in the postanesthesia care unit (PACU).

Methods

Over 3 months, 2,031 patients were observed, and each task/activity related to direct patient care was recorded and assigned points according to the Project Research in Nursing (PRN) workload system. PRN values for each patient were merged with data from an anesthesia database containing demographics, anesthesia technique, and postoperative adverse events. Mean and median PRN points were determined by age, sex, duration of procedure, and mode of anesthesia for patients with and without adverse events in the PACU. Three theoretical models were developed to determine the effect of differing rates of adverse events on the requirements for nurses in the PACU.

Results

The median workload (PRN points) per patient was 31.0 (25th-75th percentile, 25-46). Median workload was 26 points for patients with no postoperative events and 155 for > or = six adverse events. Workload varied by type of postoperative event (e.g., unanticipated admission to the intensive care unit, median workload = 95; critical respiratory event = 54; and nausea/vomiting = 33). Monitored anesthesia care or general anesthesia with spontaneous ventilation used less resources compared with general anesthesia with mechanical ventilation. Modeling various scenarios (controlling for types of patients) showed that adverse events increased the number of nursing personnel required in the PACU.

Conclusions

Nursing care documentation based on requirements for individual patients demonstrates that the rate of postoperative adverse events affects the amount of nursing resources needed in the PACU.
Minidose Bupivacaine–Fentanyl Spinal Anesthesia for Surgical Repair of Hip Fracture in the Aged
Authors: Ben-David Bruce , Frankel Roman , Arzumonov Tatianna , Marchevsky Yuri , Volpin Gershon
Published: November 2003

Background

Spinal anesthesia for surgical repair of hip fracture in the elderly is associated with a high incidence of hypotension. The synergism between intrathecal opioids and local anesthetics may make it possible to achieve reliable spinal anesthesia with minimal hypotension using a minidose of local anesthetic.

Methods

Twenty patients aged > or = 70 yr undergoing surgical repair of hip fracture were randomized into two groups of 10 patients each. Group A received a spinal anesthetic of bupivacaine 4 mg plus fentanyl 20 microg, and group B received 10 mg bupivacaine. Hypotension was defined as a systolic pressure of < 90 mmHg or a 25% decrease in mean arterial pressure from baseline. Hypotension was treated with intravenous ephedrine boluses 5-10 mg up to a maximum 50 mg, and thereafter by phenylephrine boluses of 100-200 microg.

Results

All patients had satisfactory anesthesia. One of 10 patients in group A required ephedrine, a single dose of 5 mg. Nine of 10 patients in group B required vasopressor support of blood pressure. Group B patients required an average of 35 mg ephedrine, and two patients required phenylephrine. The lowest recorded systolic, diastolic, and mean blood pressures as fractions of the baseline pressures were, respectively, 81%, 84%, and 85% versus 64%, 69%, and 64% for group A versus group B.

Conclusions

A "minidose" of 4 mg bupivacaine in combination with 20 microg fentanyl provides spinal anesthesia for surgical repair of hip fracture in the elderly. The minidose combination caused dramatically less hypotension than 10 mg bupivacaine and nearly eliminated the need for vasopressor support of blood pressure.
Neuromuscular Effects of Mivacurium in 2- to 12-yr-old Children with Burn Injury
Authors: Martyn J. A. J. , Goudsouzian Nishan G. , Chang YuChiao , Szyfelbein Stanislaw K. , Schwartz Ann E. , Patel Sanjay S.
Published: November 2003

Background

Burned patients are usually resistant to the neuromuscular effects of nondepolarizing relaxants, mostly because of receptor changes. The magnitude of the resistance is related to burn size and time after burn. Mivacurium is a muscle relaxant, degraded by plasma cholinesterase, whose enzyme activity is decreased in burns. The present study tested the hypothesis that burn-induced depressed plasma cholinesterase activity counteracts the receptor-mediated resistance, resulting in a lack of resistance to mivacurium.

Methods

Burned patients (n = 23), aged 2-12 yr, subclassified into burns of 10-30% or > 30% of body surface, were studied at < or = 6 days and again at 1-12 weeks after burn if possible. Thirteen additional patients served as controls. Neuromuscular variables monitored included onset and recovery following bolus dose, continuous infusion rates required to maintain 95 +/- 4% paralysis, and recovery rates following infusion.

Results

The onset times of maximal twitch suppression were not different between burns and controls, but recovery to 25% of baseline twitch height was prolonged in patients with > 30% burn irrespective of time after injury. The continuous infusion rates to maintain twitch suppression at 95 +/- 4% were not different between groups. The recovery indices, including train-of-four to > 75%, 25-75%, or 5-95% in burned patients, were similar or prolonged compared with controls. The prolonged recovery in burned patients was inversely related to plasma cholinesterase activity (R2 = 0.86, r = -0.93, P < 0.001), and the decreased plasma cholinesterase activity was related to burn size and time after burn.

Conclusions

A normal mivacurium dosage (0.2 mg/kg) effects good relaxation conditions in burned patients, with an onset time similar to that in controls. This finding contrasts with the response seen with other nondepolarizing drugs, higher doses of which are required to effect paralysis. The decreased metabolism of mivacurium, resulting from depressed plasma cholinesterase activity, probably counteracts the receptor-mediated potential for resistance. Because succinylcholine is contraindicated in burned patients, larger doses of nondepolarizing agents are advocated to effect rapid onset of paralysis. This generalization does not hold for mivacurium. diatrics; plasma cholinesterase; relaxant resistance; succinylcholine, alternative to.)
Racemic Ketamine Decreases Muscle Sympathetic Activity but Maintains the Neural Response to Hypotensive Challenges in Humans
Authors: Kienbaum Peter , Heuter Thorsten , Michel Martin C. , Peters Jürgen
Published: November 2003

Background

Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent sympathetic nerve activity have not been performed in humans. The authors tested the hypothesis that racemic ketamine increases efferent muscle sympathetic activity (MSA) and maintains the muscle sympathetic response to hypotensive challenges.

Methods

Muscle sympathetic activity was recorded by microneurography in the peroneal nerve of six healthy subjects before and during anesthesia with racemic ketamine (2 mg/kg intravenously plus 30 microg x kg(-1) x min(-1)). Catecholamine plasma concentrations, heart rate, and blood pressure were also determined. Muscle sympathetic neural responses to a hypotensive challenge were assessed by injection of sodium nitroprusside (2-10 microg/kg) before and during ketamine anesthesia. In the final step, increased arterial pressure observed during ketamine anesthesia was adjusted to preanesthetic baseline by sodium nitroprusside infusion (1-6 microg x kg(-1) x min(-1)).

Results

Ketamine significantly decreased MSA burst frequency (mean +/- SD, 18 +/- 9 bursts/min to 9 +/- 8 bursts/min) and burst incidence (26 +/- 11 bursts/100 heart beats to 9 +/- 6 bursts/100 heart beats). However, when increased mean arterial pressure (85 +/- 8 mmHg to 121 +/- 20 mmHg) was normalized to the awake baseline by sodium nitroprusside, MSA recovered (25 +/- 18 bursts/min; 23 +/- 14 bursts/100 heart beats). During ketamine anesthesia, both epinephrine (15 +/- 10 pg/ml to 256 +/- 193 pg/ml) and norepinephrine (250 +/- 105 pg/ml to 570 +/- 270 pg/ml) plasma concentrations significantly increased, as did heart rate (67 +/- 13 beats/min to 113 +/- 15 beats/min). Hypotensive challenges similarly increased MSA both in the awake state and during ketamine anesthesia.

Conclusions

During increased arterial blood pressure associated with ketamine, sympathetic discharge to muscle blood vessels decreases at the same time that plasma concentrations of norepinephrine increase. When this increase in arterial blood pressure is reversed, MSA during ketamine is not changed from preketamine baseline recordings. Finally, hypotensive challenges still evoke an unchanged sympathetic reflex response. Thus, our results do not support the assumption that ketamine anesthesia increases sympathetic nerve activity in a generalized fashion.
In Vitro Effects of Desflurane, Sevoflurane, Isoflurane, and Halothane in Isolated Human Right Atria
Authors: Hanouz Jean-Luc , Massetti Massimo , Guesne Géraldine , Chanel Stéphane , Babatasi Gérard , Rouet René , Ducouret Pierre , Khayat André , Galateau Françoise , Bricard Henri , Gérard Jean-Louis
Published: November 2003

Background

Direct myocardial effects of volatile anesthetics have been studied in various animal species in vitro. This study evaluated the effects of equianesthetic concentrations of desflurane, sevoflurane, isoflurane, and halothane on contractile parameters of isolated human atria in vitro.

Methods

Human right atrial trabeculae, obtained from patients undergoing coronary bypass surgery, were studied in an oxygenated (95% O2-5% CO2) Tyrode's modified solution ([Ca2+]o = 2.0 mM, 30 degrees C, stimulation frequency 0.5 Hz). The effects of equianesthetic concentrations (0.5, 1, 1.5, 2, and 2.5 minimum alveolar concentration [MAC]) of desflurane, sevoflurane, isoflurane, and halothane on inotropic and lusitropic parameters of isometric twitches were measured.

Results

Isoflurane, sevoflurane, and desflurane induced a moderate concentration-dependent decrease in active isometric force, which was significantly lower than that induced by halothane. In the presence of adrenoceptor blockade, the desflurane-induced decrease in peak of the positive force derivative and time to peak force became comparable to those induced by isoflurane. Halothane induced a concentration-dependent decrease in time to half-relaxation and a contraction-relaxation coupling parameter significantly greater than those induced by isoflurane, sevoflurane and desflurane.

Conclusions

In isolated human atrial myocardium, desflurane, sevoflurane, and isoflurane induced a moderate concentration-dependent negative inotropic effect. The effect of desflurane on time to peak force and peak of the positive force derivative could be related to intramyocardial catecholamine release. At clinically relevant concentrations, desflurane, sevoflurane, and isoflurane did not modify isometric relaxation.
Neuronal Nitric Oxide Synthase Mediates Halothane-induced Cerebral Microvascular Dilation
Authors: Staunton Michael , Drexler Cathy , Schmid Phillip G. , Havlik Heather S. , Hudetz Antal G. , Farber Neil E.
Published: November 2003

Background

The causes of volatile anesthetic-induced cerebral vasodilation include direct effects on smooth muscle and indirect effects via changes in metabolic rate and release of mediators from vascular endothelium and brain parenchyma. The role of nitric oxide and the relative importance of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) are unclear.

Methods

Rat brain slices were superfused with oxygenated artificial cerebrospinal fluid. Hippocampal arteriolar diameters were measured using computerized videomicrometry. Vessels were preconstricted with prostaglandin F2alpha (PGF2alpha; halothane group) or pretreated with 7-nitroindazole sodium (7-NINA, specific nNOS inhibitor, 7-NINA + halothane group) or N-nitro-L-arginine methylester (L-NAME; nonselective NOS inhibitor, L-NAME + halothane group) and subsequently given PGF2alpha to achieve the same total preconstriction as in the halothane group. Increasing concentrations of halothane were administered and vasodilation was calculated as a percentage of preconstriction.

Results

Halothane caused significant, dose-dependent dilation of hippocampal microvessels (halothane group). Inhibition of nNOS by 7-NINA or nNOS + eNOS by L-NAME similarly attenuated halothane-induced dilation at 0.6, 1.6, and 2.6% halothane. The dilation (mean +/- SEM) at 1.6% halothane was 104 +/- 10%, 65 +/- 6%, and 51 +/- 9% in the halothane, 7-NINA + halothane and L-NAME + halothane groups, respectively. The specificity of 7-NINA was confirmed by showing that acetylcholine-induced dilation was not inhibited by 7-NINA but was converted to constriction by L-NAME.

Conclusions

At clinically relevant concentrations, halothane potently dilates intracerebral arterioles. This dilation is mediated, in part, by neuronally derived nitric oxide. Endothelial NOS does not play a major role in halothane-induced dilation of hippocampal microvessels.