bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirements for Muscle Relaxants during Radical Retropubic Prostatectomy
Authors: King Melinda , Sujirattanawimol Nuntiya , Danielson David R. , Hall Brian A. , Schroeder Darrell R. , Warner David O.
Published: November 2003

Background

The need for the routine use of muscle relaxants to provide an adequate surgical field for intraabdominal surgery has not been established. This study tested the hypothesis that vecuronium decreases the frequency of unacceptable operating conditions for patients undergoing radical retropubic prostatectomy who are anesthetized with isoflurane and fentanyl.

Methods

After obtaining informed consent, patients in this blinded, placebo-controlled study were randomized to receive either an infusion of vecuronium or saline (placebo) beginning 5 min after fascial incision during the maintenance of anesthesia with at least 1 minimum alveolar concentration end-tidal isoflurane and fentanyl infusion. The surgical field was graded from 1 (excellent) to 4 (unacceptable) by the surgeons at 15-min intervals. If a grade 4 rating occurred (defined as a treatment failure), the patient received rescue vecuronium.

Results

A total of 120 patients are included in this report (59 in the vecuronium group and 61 in the placebo group). The frequency of treatment failure in the placebo group was 17 of 61 (27.9%) versus 1 of 59 (1.7%) in the control group who received vecuronium (P < 0.001). Thirty-eight patients (62.3%) in the placebo group and 52 patients (88.1%) in the vecuronium group had surgical field ratings of < or = 2 (good to excellent) at each time assessed throughout the procedure.

Conclusion

The study hypothesis was confirmed. However, an isoflurane-fentanyl anesthetic alone produced a good to excellent surgical field in approximately two thirds of patients undergoing radical retropubic prostatectomy without the use of muscle relaxants. Thus, the routine use of muscle relaxants in adequately anesthetized patients undergoing this procedure may not be indicated.
Effects of Mechanical Ventilation on Release of Cytokines into Systemic Circulation in Patients with Normal Pulmonary Function
Authors: Wrigge Hermann , Zinserling Jörg , Stüber Frank , von Spiegel Tilman , Hering Rudolf , Wetegrove Silke , Hoeft Andreas , Putensen Christian
Published: November 2003

Background

Mechanical ventilation with high tidal volumes (V(T)) in contrast to mechanical ventilation with low V(T) has been shown to increase plasma levels of proinflammatory and antiinflammatory mediators in patients with acute lung injury. The authors hypothesized that, in patients without previous lung injury, a conventional potentially injurious ventilatory strategy with high V(T) and zero end-expiratory pressure (ZEEP) will not cause a cytokine release into systemic circulation.

Methods

A total of 39 patients with American Society of Anesthesiologists physical status I-II and without signs of systemic infection scheduled for elective surgery with general anesthesia were randomized to receive mechanical ventilation with either (1) V(T) = 15 ml/kg ideal body weight on ZEEP, (2) V(T) = 6 ml/kg ideal body weight on ZEEP, or (3) V(T) = 6 ml/kg ideal body weight on positive end-expiratory pressure of 10 cm H2O. Plasma levels of proinflammatory and antiinflammatory mediators tumor necrosis factor, interleukin (IL)-6, IL-10, and IL-1 receptor antagonist were determined before and 1 h after the initiation of mechanical ventilation.

Results

Plasma levels of all cytokines remained low in all settings. IL-6, tumor necrosis factor, and IL-1 receptor antagonist did not change significantly after 1 h of mechanical ventilation. IL-10 was below the detection limit (10 pg/ml) in 35 of 39 patients. There were no differences between groups.

Conclusions

Initiation of mechanical ventilation for 1 h in patients without previous lung injury caused no consistent changes in plasma levels of studied mediators. Mechanical ventilation with high V(T) on ZEEP did not result in higher cytokine levels compared with lung-protective ventilatory strategies. Previous lunge damage seems to be mandatory to cause an increase in plasma cytokines after 1 h of high V(T) mechanical ventilation.
Elevated Thermostatic Setpoint in Postoperative Patients
Authors: Frank Steven M. , Kluger Matthew J. , Kunkel Steven L.
Published: November 2003

Background

The mechanism and clinical relevance of increased core temperature (Tc) after surgery are poorly understood. Because fever is used as a diagnostic sign of infection, it is important to recognize what constitutes the normal postoperative thermoregulatory response. In the current study the authors tested the hypothesis that a regulated increase in Tc setpoint occurs after surgery.

Methods

The authors prospectively studied 271 patients in the first 24 h after a variety of vascular, abdominal, and thoracic surgical procedures. Tc measured in the urinary bladder, skin-surface temperatures, thermoregulatory responses (vasoconstriction and shivering), and total leukocyte counts were assessed. In a subset of 34 patients, plasma concentrations of tumor necrosis factor, interleukin (IL)-6, and IL-8 were measured before and after surgery.

Results

In the early postoperative period, the maximum increase in Tc above the preoperative baseline averaged 1.4 +/- 0.8 degrees C (2.5 +/- 1.4 degrees F), with the Tc peak occurring 11.1 /- 5.8 h after surgery. Fifty percent of patients had a maximum Tc greater than or equal to 38.0 degrees C (100.4 degrees F) and 25% had a maximum Tc greater than or equal to 38.5 degrees C (101.3 degrees F). The progressive postoperative increase in Tc was clearly associated with cutaneous vasoconstriction and shivering, indicating a regulated elevation in Tc setpoint. The elevated Tc was associated with an increased IL-6 response but not with leukocytosis. Maximum postoperative Tc was positively correlated with duration and extent of the surgical procedure.

Conclusions

A regulated elevation in Tc setpoint (fever) occurs normally after surgery. The association between Tc elevation, extent and duration of surgery, and the cytokine response suggests that early postoperative fever is a manifestation of perioperative stress.
Rapid Hypothermic Aortic Flush Can Achieve Survival without Brain Damage after 30 Minutes Cardiac Arrest in Dogs
Authors: Behringer Wilhelm , Prueckner Stephan , Kentner Rainer , Tisherman Samuel A. , Radovsky Ann , Clark Robert , Stezoski S. William , Henchir Jeremy , Klein Edwin , Safar Peter
Published: November 2003

Background

Neither exsanguination to pulselessness nor cardiac arrest of 30 min duration can be reversed with complete neurologic recovery using conventional resuscitation methods. Techniques that might buy time for transport, surgical hemostasis, and initiation of cardiopulmonary bypass or other resuscitation methods would be valuable. We hypothesized that an aortic flush with high-volume cold normal saline solution at the start of exsanguination cardiac arrest could rapidly preserve cerebral viability during 30 min of complete global ischemia and achieve good outcome.

Methods

Sixteen dogs weighing 20-25 kg were exsanguinated to pulselessness over 5 min, and circulatory arrest was maintained for another 30 min. They were then resuscitated using closed-chest cardiopulmonary bypass and had assisted circulation for 2 h, mild hypothermia (34 degrees C) for 12 h, controlled ventilation for 20 h, and intensive care to outcome evaluation at 72 h. Two minutes after the onset of circulatory arrest, the dogs received a flush of normal saline solution at 4 degrees C into the aorta (cephalad) via a balloon catheter. Group I (n = 6) received a flush of 25 ml/kg saline with the balloon in the thoracic aorta; group II (n = 7) received a flush of 100 ml/kg saline with the balloon in the abdominal aorta.

Results

The aortic flush decreased mean tympanic membrane temperature (Tty) in group I from 37.6 +/- 0.1 to 33.3 +/- 1.6 degrees C and in group II from 37.5 +/- 0.1 to 28.3 +/- 2.4 degrees C (P = 0.001). In group 1, four dogs achieved overall performance category (OPC) 4 (coma), and 2 dogs achieved OPC 5 (brain death). In group II, 4 dogs achieved OPC 1 (normal), and 3 dogs achieved OPC 2 (moderate disability). Median (interquartile range [IQR]) neurologic deficit scores (NDS 0-10% = normal; NDS 100% = brain death) were 69% (56-99%) in group I versus 4% (0-15%) in group II (P = 0.003). Median total brain histologic damage scores (HDS 0 = no damage; > 100 = extensive damage; 1,064 = maximal damage) were 144 (74-168) in group I versus 18 (3-36) in group II (P = 0.004); in three dogs from group II, the brain was histologically normal (HDS 0-5).

Conclusions

A single high-volume flush of cold saline (4 degrees C) into the abdominal aorta given 2 min after the onset of cardiac arrest rapidly induces moderate-to-deep cerebral hypothermia and can result in survival without functional or histologic brain damage, even after 30 min of no blood flow.
Effects of Propofol on H-reflex in Humans
Authors: Kerz Thomas , Hennes Hans-Jürgen , Fève Annaïk , Decq Philippe , Filipetti Paul , Duvaldestin Philippe
Published: November 2003

Background

Depression of spinal cord motoneuron excitability has been proposed to contribute to surgical immobility. The H-reflex, which measures alpha-motoneuron excitability, is depressed by volatile anesthetics, whereas the action of propofol is unknown. The objective of this study was to determine the effects of propofol anesthesia on the H-reflex.

Methods

In 13 patients (group 1), H-reflex was measured before (T0), 3 min after (T1), and 10 min after (T2) a 2-mg/kg bolus dose of propofol, followed by an infusion of 10 mg x kg(-1) x h(-1). Ten patients (group 2) were studied when propofol was given via a programmable pump set to a propofol blood concentration of 6 microg/ml, and 10 patients (group 3) were studied with the pump set to 9 microg/ml. Latencies and amplitudes of H-reflexes (H0, H1, H2) and M-responses (M0, M1, M2) of the soleus muscle were recorded, and H/M ratios (H0/M0, H1/M1, H2/M2) were calculated.

Results

In group 1, H-reflex amplitudes and the H/M ratio were diminished after induction with propofol (H0 vs. H1, P = 0.033; H0/M0 vs. H1/M1, P = 0.042). After 10 min of propofol infusion, the H2/M2 ratio was still decreased versus H0/M0 (P = 0.031). In group 2, no difference was detected. In group 3, propofol depressed H-reflex amplitudes at T2 (H0 vs. H2, P < 0.01), and amplitudes were also lower at T2 than at T1 (H1 vs. H2, P < 0.01). In this group, the H/M ratio decreased from T0 to T2 (H0/M0 vs. H2/M2, P < 0.002).

Conclusions

During steady state conditions using propofol as the sole agent, a depression of the H-reflex is observed only at a high blood concentration of 9 microg/ml. The authors suggest that immobility during propofol anesthesia is not caused by a depression of spinal motoneuron circuit excitability.
Electrocardiographic Exercise Stress Testing for Cardiac Risk Assessment in Patients Undergoing Noncardiac Surgery
Authors: Gauss Albrecht , Röhm Hans-Jörg , Schäuffelen Andreas , Vogel Thomas , Mohl Ulrich , Straehle Andreas , Meierhenrich Rainer , Georgieff Michael , Steinbach Gerald , Schütz Wolfram
Published: November 2003

Background

The value of exercise electrocardiography in the prediction of perioperative cardiac risk has yet to be defined. This study was performed to determine the predictive value of exercise electrocardiography as compared with clinical parameters and resting electrocardiography.

Methods

A total of 204 patients at intermediate risk for cardiac complications prospectively underwent exercise electrocardiography before noncardiac surgery. Of these, 185 were included in the final evaluation. All patients underwent follow-up evaluation postoperatively by Holter monitoring for 2 days, daily 12-lead electrocardiogram, and creatine kinase, creatine kinase MB, and troponin-T measurements for 5 days. Cardiac events were defined as cardiac death, myocardial infarction, minor myocardial cell injury, unstable angina pectoris, congestive heart failure, and ventricular tachyarrhythmia. Potential risk factors for an adverse event were identified by univariate and multivariate logistic regression analysis.

Results

Perioperative cardiac events were observed in 16 patients. There were 6 cases of myocardial infarction and 10 cases of myocardial cell injury. The multivariate correlates of adverse cardiac events were definite coronary artery disease (odds ratio, 8.8; 95% confidence interval [CI], 1.1--73.1; P = 0.04), major surgery (odds ratio, 4.7; 95% CI, 1.3--16.3; P = 0.02), reduced left ventricular performance (odds ratio, 2.0; 95% CI, 1.1--3.8; P = 0.03), and ST-segment depression of 0.1 mV or more in the exercise electrocardiogram (odds ratio, 5.2; 95% CI, 1.5--18.5; P = 0.01). A combination of clinical variables and exercise electrocardiography improved preoperative risk stratification.

Conclusions

This prospective study shows that a ST-segment depression of 0.1 mV or more in the exercise electrocardiogram is an independent predictor of perioperative cardiac complications.
Pharmacodynamics of Orally Administered Sustained- release Hydromorphone in Humans
Authors: Angst Martin S. , Drover David R. , Lötsch Jörn , Ramaswamy Bhamini , Naidu Sujata , Wada D. Russell , Stanski Donald R.
Published: November 2003

Background

The disposition kinetics of hydromorphone generally necessitates oral administration every 4 h of the conventional immediate-release tablet to provide sustained pain relief. This trial examined time course and magnitude of analgesia to experimental pain after administration of sustained-release hydromorphone as compared with that after immediate-release hydromorphone or placebo.

Methods

Using a 4 x 4 Latin square double-blind design, 12 subjects were randomized to receive a single dose of 8, 16, and 32 mg sustained-release hydromorphone and placebo. The same subjects had received 8 mg immediate-release hydromorphone before this study. Using an electrical experimental pain paradigm, analgesic effects were assessed for up to 30 h after administration, and venous hydromorphone plasma concentrations were measured at corresponding times.

Results

The hydromorphone plasma concentration peaked significantly later (12.0 h [12.0--18.0] vs. 0.8 h [0.8--1.0]; median and interquartile range) but was maintained significantly longer at greater than 50% of peak concentration (22.7 +/- 8.2 h vs. 1.1 +/- 0.7 h; mean +/- SD) after sustained-release than after immediate-release hydromorphone. Similarly, sustained-release hydromorphone produced analgesic effects that peaked significantly later (9.0 h [9.0--12.0] vs. 1.5 h [1.0--2.0]) but were maintained significantly longer at greater than 50% of peak analgesic effect (13.3 +/- 6.3 h vs. 3.6 +/- 1.7 h). A statistically significant linear relation between the hydromorphone plasma concentration and the analgesic effect on painful stimuli existed.

Conclusion

A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.
Perioperative Activation of Hemostasis in Vascular Surgery Patients
Authors: Marc Samama Charles , Thiry Dominique , Elalamy Ismael , Diaby Mohamed , Guillosson Jean-Jacques , Kieffer Edouard , Coriat Pierre
Published: November 2003

Background

Perioperative activation of hemostasis could play an important role in the occurrence of postoperative cardiac events. The authors conducted a prospective study to assess platelet function, coagulation, and fibrinolysis status during and after infrarenal aortic surgery.

Methods

Seventeen patients were studied. Excluded were patients with preoperative coagulopathies or liver disease, or cardiac or renal insufficiency; patients receiving anticoagulant treatment, antiplatelet agents, nonsteroidal antiinflammatory agents, fresh frozen plasma, or platelet concentrates; and patients undergoing reoperation and septic patients. Blood samples were drawn before induction (T1), 1 h after incision (T2), 1 h after extubation (T3), 24 h postoperatively (T4), 48 h postoperatively (T5), and at day 7 (T6). The following tests were performed: platelet count, platelet aggregation, platelet flow cytometry for CD62 and CD63, usual coagulation tests, thrombin--antithrombin complexes, plasminogen activator inhibitor 1.

Results

A significant increase of adenosine diphosphate--induced platelet aggregation was observed postoperatively at T4 and T5. This was not associated with a change of flow cytometry profile. No increase of thrombin--antithrombin complex levels was observed. A higher fibrinogen rate was detected at T5 and T6. Greater amounts of plasminogen activator inhibitor 1 were detected at T3 and T4. Thus, thrombin generation was limited and fibrinolysis was impaired postoperatively. Platelets were not activated in the postoperative period, as shown by flow cytometry, but were prone to be activated, as shown by aggregation studies.

Conclusion

The association of more easily activated platelets with a higher fibrinogen rate and a temporary shut down of fibrinolysis during the early postoperative period may indicate an increased thrombotic risk in patients undergoing major vascular surgery.
The Combitube in Elective Surgery
Authors: Gaitini Luis A. , Vaida Sonia J. , Mostafa Somri , Yanovski Boris , Croitoru Milian , Capdevila Marisa D. , Sabo Edmond , Ben-David Bruce , Benumof Jonathan
Published: November 2003

Background

The Combitube has proved to be a valuable device for securing the airway in cases of difficult intubation. This study investigated the effectiveness of the Combitube in elective surgery during both mechanical and spontaneous ventilation.

Methods

Two hundred patients classified as American Society of Anesthesiologists physical status I and II, with normal airways, scheduled for elective surgery were randomly allocated into two groups: nonparalyzed, spontaneously breathing (n = 100); or paralyzed, mechanically ventilated (n = 100). After induction of general anesthesia and insertion of the Combitube, oxygen saturation, end-tidal carbon dioxide and isoflurane concentration, systolic and diastolic blood pressure and heart rate, as well as breath-by-breath spirometry data were obtained every 5 min.

Results

In 97% of patients, it was possible to maintain oxygenation, ventilation, and respiratory mechanics, as well as hemodynamic stability during either mechanical or spontaneous ventilation for the entire duration of surgery. The duration of surgery was between 15 and 155 min.

Conclusions

The results of this study suggest that the Combitube is an effective and safe airway device for continued management of the airway in 97% of elective surgery cases.
Study of the “Sniffing Position” by Magnetic Resonance Imaging
Authors: Adnet Frédéric , Borron Stephen W. , Dumas Jean Luc , Lapostolle Frédéric , Cupa Michel , Lapandry Claude
Published: November 2003

Background

The "sniffing position" is widely considered essential to the performance of orotracheal intubation and has become the cornerstone of training in anesthesiology. However, the anatomic superiority of this patient head position has not been established.

Methods

Eight healthy young adult volunteers underwent magnetic resonance imaging scanning in three anatomic positions: head in neutral position, in simple extension, and in the "sniffing position" (neck flexed and head extended by means of a pillow). The following measurements were made on each scan: (1) the axis of the mouth (MA); (2) the pharyngeal axis (PA); (3) the laryngeal axis (LA); and (4) the line of vision. The various angles between these axes were defined: alpha angle between the MA and PA, beta angle between PA and LA, and delta angle between line of vision and LA.

Results

Both simple extension and sniffing positions significantly improved (P < 0.05) the delta angle associated with best laryngoscopic view. Our results show that the beta value increases significantly (P < 0.05) when the head position is shifted from the neutral position (beta = 7 +/- 6 degrees ) to the sniffing position (beta = 13 +/- 6 degrees ), and the alpha value slightly (but significantly) decreases (from 87 +/- 10 degrees to 63 +/- 11 degrees; P < 0.05). Anatomic alignment of the LA, PA, and MA axes is impossible to achieve in any of the three positions tested. There were no significant differences between angles observed in simple extension and sniffing positions.

Conclusions

The sniffing position does not achieve alignment of the three important axes (MA, PA, and LA) in awake patients with normal airway anatomy.
Perfluorohexane Attenuates Proinflammatory and Procoagulatory Response of Activated Monocytes and Alveolar Macrophages
Authors: Koch Thea , Ragaller Maximilian , Haufe Dirk , Hofer Andreas , Grosser Marianne , Albrecht Detlev M. , Kotzsch Matthias , Luther Thomas
Published: November 2003

Background

A number of studies have demonstrated the effectiveness of liquid ventilation with perfluorocarbons in improving pulmonary function in acute respiratory distress syndrome. Although it is known that perfluorocarbon-associated gas exchange facilitates lung mechanics and oxygenation, the complete mechanism by which perfluorocarbons exert their beneficial effects in acute lung injury still remains unclear. Possibly, an influence of perfluorocarbons on proinflammatory and procoagulant features of monocytic cells present in the alveolar space, such as alveolar macrophages (AMs), may be involved. Therefore, we examined in an in vitro model the effects of perfluorocarbon on both activated mononuclear blood cells (MBCs) and AMs by monitoring the expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF)alpha, and tissue factor (TF).

Methods

Mononuclear blood cells, obtained from peripheral blood of healthy volunteers, or AMs from diagnostic bronchoalveolar lavage were stimulated by incubation with lipopolysaccharide in the presence of different amounts of perfluorohexane, which was devoid of cytotoxicity.

Results

Using both video-enhanced contrast and electron microscopy, the authors observed that perfluorohexane droplets were phagocytosed by activated monocytes as well as by in vitro--cultured AMs within 1--3 h. After lipopolysaccharide stimulation of monocytes or AMs, we observed a down-regulation of TF mRNA and a significant inhibition (P < 0.05) of cellular TF antigen by perfluorohexane. In addition, the concentration of both IL-1 beta and TNF alpha in the supernatant of lipopolysaccharide-stimulated MBC was significantly decreased (P < 0.01) by perfluorohexane compared with controls without perfluorohexane. By preincubation of lipopolysaccharide-containing medium with perfluorohexane, the authors could exclude that the inhibitory effect of perfluorohexane was caused by binding or sequestering limited amounts of lipopolysaccharide.

Conclusion

Taken together, our results demonstrate an interference of perfluorohexane with the expression of the procoagulant protein TF on monocytes and AMs as well as with the release of proinflammatory cytokines by MBCs. These effects may contribute to the protective role of liquid ventilation with perfluorocarbons in injuries associated with local activation of inflammatory processes.
Anesthetic-like Interaction of the Sleep-inducing Lipid Oleamide with Voltage-gated Sodium Channels in Mammalian Brain
Authors: Nicholson Russell A. , Zheng Jian , Robin Ganellin C. , Verdon Bernard , Lees George
Published: November 2003

Background

cis-9,10-Octadecenoamide (cOA) accumulates in cerebrospinal fluid during sleep deprivation and induces sleep in animals, but its cellular actions are poorly characterized. In earlier studies, like a variety of anesthetics, cOA modulated gamma-aminobutyric acidA receptors and inhibited transmitter release/burst firing in cultured neurones or synaptoneurosomes.

Methods

Here, radioligand binding ([3H]batrachotoxinin A 20-alpha-benzoate and mouse central nervous system synaptoneurosomes) and voltage clamp (whole cell recording from cultured NIE115 murine neuroblastoma) confirmed an interaction with neuronal voltage-gated sodium channels (VGSC).

Results

cOA stereoselectively inhibited specific binding of toxin to VGSC (inhibitor concentration that displaces 50% of specifically bound radioligand, 39.5 microm). cOA increased (4x) the Kd of toxin binding without affecting its binding maximum. Rate of dissociation of radioligand was increased without altering association kinetics, suggesting an allosteric effect (indirect competition at site 2 on VGSC). cOA blocked tetrodotoxin-sensitive sodium currents (maximal effect and affinity were significantly greater at depolarized potentials; P < 0.01). Between 3.2 and 64 microm, the block was concentration-dependent and saturable, but cOA did not alter the V50 for activation curves or the measured reversal potential (P > 0.05). Inactivation curves were significantly shifted in the hyperpolarizing direction by cOA (maximum, -15.4 +/- 0.9 mV at 32 microm). cOA (10 microm) slowed recovery from inactivation, with tau increasing from 3.7 +/- 0.4 ms to 6.4 +/- 0.5 ms (P < 0.001). cOA did not produce frequency-dependent facilitation of block (up to 10 Hz).

Conclusions

These effects (and the capacity of oleamide to modulate gamma-aminobutyric acidA receptors in earlier studies) are strikingly similar to those of a variety of anesthetics. Oleamide may represent an endogenous ligand for depressant drug sites in mammalian brain.
Halothane Increases Smooth Muscle Protein Phosphatase in Airway Smooth Muscle
Authors: Hanazaki Motohiko , Jones Keith A. , Perkins William J. , Warner David O.
Published: November 2003

Background

Halothane relaxes airway smooth muscle, in part, by decreasing the force produced for a given intracellular [Ca(2+)] (i.e., Ca(2+) sensitivity) during muscarinic stimulation, an effect produced by a decrease in regulatory myosin light-chain (rMLC) phosphorylation. The authors tested the hypothesis that halothane reduces rMLC phosphorylation during muscarinic stimulation at constant intracellular [Ca(2+)] by increasing smooth muscle protein phosphatase (SMPP) activity, without changing myosin light-chain kinase (MLCK) activity.

Methods

Enzyme activities were assayed in beta-escin permeabilized strips of canine tracheal smooth muscle. Under conditions of constant intracellular [Ca(2+)], the rate of rMLC phosphorylation was measured by Western blotting during inhibition of SMPP with microcystin-LR (to assay MLCK activity) or during inhibition of MLCK by wortmannin and adenosine triphosphate depletion (to assay SMPP activity). The effect of halothane (0.8 mm) on enzyme activities and isometric force during stimulation with 0.6 microm Ca(2+) and 10 microm acetylcholine was determined.

Results

Halothane produced a 14 +/- 8% (mean +/- SD) decrease in isometric force by significantly reducing rMLC phosphorylation (from 32 +/- 9% to 28 +/- 9%). Halothane had no significant effect on any parameter of a monoexponential relation fit to the data for the MLCK activity assay. In contrast, halothane significantly decreased the half-time for rMLC dephosphorylation in the SMPP activity assay (from 0.74 +/- 0.28 min to 0.44 +/- 0.10 min), indicating that it increased SMPP activity.

Conclusions

Halothane decreases Ca(2+) sensitivity and rMLC phosphorylation in airway smooth muscle during muscarinic receptor stimulation by increasing SMPP activity, without affecting MLCK, probably by disrupting receptor G-protein signaling pathways that inhibit SMPP.
Relation between Initial Blood Distribution Volume and Propofol Induction Dose Requirement
Authors: Kazama Tomiei , Ikeda Kazuyuki , Morita Koji , Ikeda Takehiko , Kikura Mutsuhito , Sato Shigehito
Published: November 2003

Background

Propofol induction dose is variable and depends on many factors, including initial volume of distribution and early disposition. The authors hypothesized that preadministration blood distribution volumes, cardiac output (CO), and hepatic blood flow (HBF) could be examined to establish a propofol induction dose.

Methods

Propofol dose required to reach loss of consciousness, when infused at infusion rate per lean body mass (LBM) of 40 mg x kg(-1) x h(-1), was determined in 75 patients aged 11-85 yr. CO, blood volume (BV), central blood volume (CBV), and HBF were measured with indocyanine green pulse spectrophotometry. Univariate least squares linear regression analysis was used to individually analyze the relation between propofol induction dose and patient characteristics, including LBM, baseline distribution volumes, CO, and HBF. Stepwise multiple linear regression models were used to select important predictors of induction dose.

Results

Although there was a significant correlation between the induction dose and each of the eight variables of age, sex, LBM, hemoglobin, CO, BV, CBV, and HBF, only factors of age (partial r = -0.655), LBM (partial r = 0.325), CBV (partial r = 0.540), and HBF (partial r = 0.357) were independently associated with the induction dose (R2 = 0.85) when all variables were included in a multivariate model.

Conclusions

At a constant propofol infusion rate of 40 mg x kg(-1) x h(-1) as a function of LBM in patients with American Society of Anesthesiologists physical status I or II, the induction dose can be determined from four variables: age, LBM, CBV, and HBF.
Opioids Inhibit Febrile Responses in Humans, Whereas Epidural Analgesia Does Not
Authors: Negishi Chiharu , Lenhardt Rainer , Ozaki Makoto , Ettinger Katharine , Bastanmehr Hiva , Bjorksten Andrew R. , Sessler Daniel I.
Published: November 2003

Background

Epidural analgesia is frequently associated with hyperthermia during labor and in the postoperative period. The conventional assumption is that hyperthermia is caused by the technique, although no convincing mechanism has been proposed. However, pain in the "control" patients is inevitably treated with opioids, which themselves attenuate fever. Fever associated with infection or tissue injury may then be suppressed by opioids in the "control" patients while being expressed normally in patients given epidural analgesia. The authors therefore tested the hypothesis that fever in humans is manifested normally during epidural analgesia, but is suppressed by low-dose intravenous opioid.

Methods

The authors studied eight volunteers, each on four study days. Fever was induced each day by 150 IU/g intravenous interleukin 2. Volunteers were randomly assigned to: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using ropivacaine alone; (3) epidural analgesia using ropivacaine in combination with 2 microg/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml.

Results

Fentanyl halved the febrile response to pyrogen, decreasing integrated core temperature from 7.0 +/- 3.2 degrees C. h on the control day, to 3.8 +/- 3.0 degrees C. h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine-fentanyl did not inhibit fever. The fraction of core-temperature measurements that exceeded 38 degrees C was halved by intravenous fentanyl, and the fraction exceeding 38.5 degrees C was reduced more than fivefold.

Conclusions

These data support the authors' proposed mechanism for hyperthermia during epidural analgesia. Fever during epidural analgesia should thus not be considered a complication of the anesthetic technique per se.
Subarachnoid Sufentanil for Early Postoperative Pain Management in Orthopedic Patients
Authors: Standl Thomas G. , Horn Ernst-Peter , Luckmann Michael , Burmeister Marc-Alexander , Wilhelm Stefan , Schulte am Esch Jochen
Published: November 2003

Background

Continuous spinal anesthesia is frequently used for intraoperative anesthesia but rarely for postoperative pain management. Because even small doses of local anesthetics can be associated with motor deficits, subarachnoid opioid injection may be an alternative.

Methods

Eighty patients randomly received a subarachnoid injection of 10 microg sufentanil, 5 mg bupivacaine, 2.5 microg sufentanil plus 2.5 mg bupivacaine, or saline through 28-gauge spinal microcatheters for early postoperative pain relief after major lower-limb surgery (n = 20 in each group). Hemodynamic and respiratory parameters, pain scores, and motor function were monitored, and sufentanil concentrations in plasma and cerebrospinal fluid were measured. Ten additional patients received up to three repetitive injections of 10 microg sufentanil over 24 h.

Results

All drugs provided excellent pain relief within 15 min after injection, lasting 128 +/- 61 min with sufentanil, 146 +/- 74 min with bupivacaine, and 167 +/- 78 min with the mixture. Patients receiving bupivacaine showed the highest cephalad extension of sensory block (median, T6) and the most intense motor block, whereas patients given only sufentanil had no motor deficit. The duration of analgesia was shorter after subsequent sufentanil injection (100-115 min) than after the first injection (198 +/- 70 min). Six of 50 patients with sufentanil experienced a short episode of respiratory depression within 30 min after the first injection. Cerebrospinal fluid concentrations of sufentanil peaked at 5 min after injection (183 +/- 167 ng/ml) but were at the level of detection in the plasma.

Conclusions

Sufentanil injected through microspinal catheters provided profound pain relief without impairing motor function when compared with bupivacaine. However, close monitoring remains mandatory in this setting.
Chlorhexidine versus Povidone Iodine in Preventing Colonization of Continuous Epidural Catheters in Children
Authors: Kinirons Brian , Mimoz Olivier , Lafendi Leila , Naas Thierry , Meunier Jean-François , Nordmann Patrice
Published: November 2003

Background

Chlorhexidine is better than povidone iodine for skin preparation before intravascular device insertion or blood culture collection, but it is not known whether chlorhexidine is superior in reducing colonization of continuous epidural catheters.

Methods

Children requiring an epidural catheter for postoperative analgesia longer than 24 h were randomly assigned to receive skin preparation with an alcoholic solution of 0.5% chlorhexidine or an aqueous solution of 10% povidone iodine before catheter insertion. Using surgical aseptic techniques, catheters were inserted into either the lumbar or the thoracic epidural space based on the preferences of the anesthesia team, on clinical indication, or both. Immediately before epidural catheter removal, their insertion site and hub were qualitatively cultures. After their removal, the catheter tips were quantitatively cultured. Catheters were classified as colonized when their tips yielded 1,000 or more colony-forming units/ml in cultures.

Results

Of 100 randomly assigned patients, 96 were evaluable. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters were kept in place for a median (range) duration of 50 (range, 21-100) h. Catheters inserted after skin preparation with chlorhexidine were one sixth as likely and less quickly to be colonized as catheters inserted after skin preparation with povidone iodine (1 of 52 catheters [0.9 per 100 catheter days] vs. 5 of 44 catheters [5.6 per 100 catheter days]; relative risk, 0.2 [95% confidence interval, 0.1-1.0]; P = 0.02). Coagulase-negative staphylococci were the only colonizing microorganisms recovered, and the skin surrounding the catheter insertion site was the origin of all the colonizing microorganisms.

Conclusions

Compared with aqueous povidone iodine, the use of alcoholic chlorhexidine for cutaneous antisepsis before epidural catheter insertion reduces the risk of catheter colonization in children.
Effect of Cricoid Pressure on the Success of Endotracheal Intubation with a Lightwand
Authors: Hodgson R. Eric , Gopalan P. Dean , Burrows Richard C. , Zuma Khangelani
Published: November 2003

Background

The lightwand may be useful as an alternative for tracheal intubation during a rapid-sequence induction of anesthesia in the presence of a full stomach. This study was undertaken to assess the effect of application of cricoid pressure on the success of lightwand intubation.

Methods

Sixty adult female patients presenting for abdominal hysterectomy were randomly allocated to lightwand intubation with and without cricoid pressure. The time to successful intubation and number of attempts were recorded.

Results

All 30 patients allocated to intubation without cricoid pressure were intubated successfully at the first attempt within a median time of 28 s (95% confidence interval, 18-77 s). Lightwand intubation with cricoid pressure was successful in 26 of 30 patients at the first attempt, but the median time to successful intubation was significantly longer at 48.5 s (95% confidence interval, 36-78 s; P = 0.001). Three patients required two attempts for successful intubation, and one could not be intubated with the lightwand while cricoid pressure was being applied.

Conclusions

The lightwand cannot be recommended for the first attempt at intubation where cricoid pressure is being applied because the time to successful intubation is significantly prolonged, and the failure rate for the first attempt at lightwand intubation is 13%.
Anesthetic Concentrations of Propofol Protect against Oxidative Stress in Primary Astrocyte Cultures
Authors: Peters Caralei E. , Korcok Jasminka , Gelb Adrian W. , Wilson John X.
Published: November 2003

Background

The extracellular concentration of glutamate in the brain increases after oxidative damage. This increase may be caused, in part, by changes in glutamate transport by astrocytes. The authors hypothesized that propofol and hypothermia mitigate the effects on astrocytes of oxidative stress.

Methods

Primary cultures of rat cerebral astrocytes were subjected to oxidative stress by incubation with tert-butyl hydroperoxide for 30 min, followed by a 30-90-min washout period. The effects of prophylactic (simultaneous with tert-butyl hydroperoxide application) and delayed (administered 30 min after the oxidant) propofol or hypothermia were determined by measuring the uptake of glutamate as well as the release of preloaded d-aspartate (a nonmetabolizable analog of glutamate) and endogenous lactate dehydrogenase (a cytosolic marker).

Results

Delayed administration of an anesthetic concentration of propofol (1-3 microm) prevented the inhibition of high-affinity glutamate uptake, stimulation of d-aspartate release, and increase in lactate dehydrogenase release caused by tert-butyl hydroperoxide (1 mm, 37 degrees C). The protective effect of propofol (EC50 = 2 microm) on glutamate uptake was 20-fold more potent than that of alpha-tocopherol (EC50 = 40 microm). Prophylactic hypothermia (28 and 33 degrees C) also protected astrocytes from tert-butyl hydroperoxide. Delayed hypothermia was not protective but did not compromise rescue by propofol.

Conclusions

Clinical levels of propofol and hypothermia mitigate the effects of oxidative stress on astrocytic uptake and retention of glutamate, with propofol having a relatively larger therapeutic window. The ability of these treatments to normalize cell transport systems may attenuate the pathologic increase in extracellular glutamate at synapses and thus prevent excitotoxic neuronal death.
Electrophysiologic Evidence for Increased Endogenous GABAergic but Not Glycinergic Inhibitory Tone in the Rat Spinal Nerve Ligation Model of Neuropathy
Authors: Kontinen Vesa K. , Stanfa Louise C. , Basu Amlan , Dickenson Anthony H.
Published: November 2003

Background

Changes in the inhibitory activity mediated by gamma-aminobutyric acid (GABA) and glycine, acting at spinal GABAA receptors and strychnine-sensitive glycine receptors, are of interest in the development of neuropathic pain. There is anatomic evidence for changes in these transmitter systems after nerve injuries, and blocking either GABAA or glycine receptors has been shown to produce allodynia-like behavior in awake normal animals.

Methods

In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal nerve ligation model of neuropathic pain were studied by comparing the effects of the GABAA-receptor antagonist bicuculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats.

Results

Bicuculline produced a dose-related facilitation of the Adelta-fiber-evoked activity in all study groups and increased C-fiber-mediated activity in the spinal nerve ligation group but not in either of the control groups. There were no differences in the effect of bicuculline on low threshold responses between the study groups. The glycine receptor antagonist strychnine did not have a statistically significant effect on any of the parameters studied in any of the control groups.

Conclusions

These results support the idea of an increased GABAergic inhibitory tone in the spinal cord of neuropathic rats, possibly as compensation for increased excitability after nerve injury.
Initial and Subsequent Dosing of Rectal Acetaminophen in Children
Authors: Birmingham, AF1-0567 Patrick K. , Tobin Michael J. , Fisher Dennis M. , Henthorn Thomas K. , Hall Steven C. , Coté Charles J.
Published: November 2003

Background

Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors' previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10-20 microg/ml, without evidence of accumulation.

Methods

Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration.

Results

All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, the target range was maintained 60 +/- 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 microg/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses.

Conclusions

A rectal acetaminophen loading dose of 40 mg/kg followed by 20-mg/kg doses every 6 h results in serum concentrations centered at the target range of 10-20 microg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.
Preoperative Anxiolysis and Postoperative Recovery in Women Undergoing Abdominal Hysterectomy
Authors: Kain Zeev N. , Sevarino Ferne B. , Rinder Christine , Pincus Sharon , Alexander Gerianne M. , Ivy Michael , Heninger George
Published: November 2003

Background

Every year, millions of patients receive sedatives for reduction of anxiety before surgery, but there is little objective data on the effect of this treatment on postoperative outcomes. To address this issue, the effects of benzodiazepine administration were evaluated in women undergoing abdominal surgery.

Methods

Patients were randomized to receive 1 mg of oral lorazepam the night before surgery and 5 mg of intramuscular midazolam on the morning of surgery (n = 34), or to receive a placebo the night before surgery and on the morning of surgery (n = 36). Postoperative pain (Visual Analogue Scale for pain, McGill Pain Questionnaire) and analgesic consumption (patient-controlled analgesia), and clinical recovery parameters such as time to discharge from hospital were evaluated after surgery.

Results

Patient-controlled analgesia use showed a marginal main effect of treatment group (F(1,51) = 2.8; P = 0.047). Post boc analysis demonstrated that patient-controlled analgesia consumption was significantly lower in the treatment group only during the first 4 h of patient-controlled analgesia use after surgery (P = 0.027). There were no significant group differences at any later postoperative time points (P = not significant). There were no group differences in the cumulative Percocet (Pfizer, New York, NY) consumption in the postoperative period (P = not significant). Further, self-reported postoperative pain did not differ significantly between groups at any of the time points (P = not significant). There were also no group differences with regard to any postoperative clinical recovery parameters.

Conclusions

Benzodiazepines administered before surgery have minimal beneficial effects on the postoperative clinical course of women undergoing abdominal hysterectomy.
Physical Factors Affecting the Production of Carbon Monoxide from Anesthetic Breakdown
Authors: Woehlck Harvey J. , Dunning Marshall , Raza Tasleem , Ruiz Franklin , Bolla Bhupinder , Zink Wolfgang
Published: November 2003

Background

Parameters determining carbon monoxide (CO) concentrations produced by anesthetic breakdown have not been adequately studied in clinical situations. The authors hypothesized that these data will identify modifiable risk factors.

Methods

Carbon monoxide concentrations were measured when partially desiccated barium hydroxide lime was reacted with isoflurane (1.5%) and desflurane (7.5%) in a Draeger Narkomed 2 anesthesia machine with a latex breathing bag substituting for a patient. Additional experiments determined the effects of carbon dioxide (0 or 350 ml/min), fresh gas flow rates (1 or 4 l/min), minute ventilation (6 or 18 l/min), or absorbent quantity (1 or 2 canisters). End-tidal anesthetic concentrations were adjusted according to a monochromatic infrared monitor.

Results

Desflurane produced approximately 20 times more CO than isoflurane when completely dried absorbents were used. Peak CO concentrations approached 100,000 ppm with desflurane. Traces of water remaining after a 66-h drying time (one weekend) markedly reduced the generation of CO compared with 2 weeks of drying. Reducing the quantity of desiccated absorbent by 50% reduced the total CO production by 40% in the first hour. Increasing the fresh gas flow rate from 1 to 4 l/min increased CO production by 67% in the first hour but simultaneously decreased average inspiratory concentrations by 53%. Carbon dioxide decreased CO production by 12% in completely desiccated absorbents.

Conclusion

Anesthetic identity, fresh gas flow rates, absorbent quantity, and water content are the most important factors determining patient exposures. Minute ventilation and carbon dioxide production by the patient are relatively unimportant.