bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Desflurane in Rat Myocardium
Authors: Gueugniaud Pierre-Yves , Hanouz Jean-Luc , Vivien Benoit , Lecarpentier Yves , Coriat Pierre , Riou Bruno
Published: November 2003

Background

The cardiovascular effects of desflurane have been investigated in several in vivo animal and human studies. To determine the possible contributions of myocardial depression, the effects of desflurane on various contractile parameters in isolated cardiac papillary muscles were compared with those of isoflurane and halothane.

Methods

The effects of desflurane, isoflurane, and halothane (0.5-2.5 minimum alveolar concentration [MAC]) were studied in rat left ventricular papillary muscles (29 degrees C; pH 7.40; stimulation frequency, 12 pulses/min). The inotropic effects were compared under low (isotony) and high (isometry) loads, using the maximum unloaded shortening velocity (Vmax) and maximum isometric active force (AF). The lusitropic effects were compared in isotonic and isometric conditions.

Results

Desflurane has no significant inotropic effect (AF at 2.5 MAC: 95 +/- 11% of control values; NS) in contrast with halothane and isoflurane (AF at 2.5 MAC: 37 +/- 14 vs. 65 +/- 10%, respectively; P < 0.05). After alpha- and beta-adrenoceptor blockade or pretreatment with reserpine, desflurane induced a negative inotropic effect (AF at 2.5 MAC: 83 +/- 11 vs. 89 +/- 8%, respectively) that was not significantly different from that of isoflurane (AF at 2.5 MAC: 80 +/- 12%). Halothane induced a negative lusitropic effect under low load, which was significantly greater than those of isoflurane and desflurane. In contrast to halothane, isoflurane and desflurane induced no significant lusitropic effect under high load and did not modify postrest potentiation. These results suggest that desflurane did not impair sarcoplasmic reticulum function.

Conclusions

When compared with isoflurane, desflurane induced a moderate positive inotropic effect related to intramyocardial catecholamine release. After adrenoceptor blockade, desflurane induced a negative inotropic effect comparable with that induced by isoflurane.
Opioid-induced Delay in Gastric Emptying
Authors: Murphy D. B. , Sutton J. A. , Prescott L. F. , Murphy M. B.
Published: November 2003

Background

Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this effect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylnaltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier.

Methods

In a randomized, double-blind, crossover placebo-controlled study, 11 healthy volunteers were given either placebo (saline), 0.09 mg/kg morphine, or 0.09 mg/kg morphine plus 0.3 mg/kg methylnaltrexone on three separate occasions before ingesting 500 ml deionized water. The rate of gastric emptying was measured by two methods: a noninvasive epigastric bioimpedance technique and the acetaminophen absorption test.

Results

The epigastric bioimpedance technique was sufficiently sensitive to detect opioid-induced changes in the rate of gastric emptying. The mean +/- SD time taken for the gastric volume to decrease to 50% (t0.5) after placebo was 5.5 +/- 2.1 min. Morphine prolonged gastric emptying to (t0.5) of 21 +/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly with morphine reversed the morphine-induced delay in gastric emptying to a t0.5 of 7.4 +/- 3.0 (P < 0.04). Maximum concentrations and area under the concentration curve from 0 to 90 min of serum acetaminophen concentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0.05). No difference in maximum concentration or area under the concentration curve from 0 to 90 min was noted between placebo and methylnaltrexone coadministered with morphine.

Conclusions

The attenuation of morphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is mediated outside the central nervous system. Methylnaltrexone may have the potential to decrease the side effects of opioid medications, which are mediated peripherally, while maintaining the central analgesia effect of the opioid.
The Addition of Phenylephrine Contributes to the Development of Transient Neurologic Symptoms after Spinal Anesthesia with 0.5% Tetracaine
Authors: Sakura Shinicki , Sumi Mariko , Sakaguchi Yasuko , Saito Yoji , Kosaka Yoshihiro , Drasner Kenneth
Published: November 2003

Background

Recent reports indicate that transient neurologic symptoms commonly occur after single-injection spinal anesthesia with lidocaine. Information regarding tetracaine has been limited to a single case report. In addition, little is known about the cause of these symptoms or the cofactors that affect their occurrence. The present study sought to determine whether the presence of phenylephrine or the concentration of glucose in the anesthetic solution affects the incidence of transient neurologic symptoms after spinal anesthesia with 0.5% tetracaine.

Methods

One-hundred sixty patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for elective surgery on a lower limb or perineum were sequentially assigned to one of four equal groups to receive intrathecal 0.5% tetracaine in 7.5% or 0.75% glucose, with or without 0.125% phenylephrine. Patients were evaluated on postoperative day one for the presence of pain, dysesthesia, or both in the legs or buttocks by an investigator unaware of the drug given.

Results

Symptoms were present in 10 patients (12.5%) receiving a spinal anesthetic containing phenylephrine, but in only one patient (1.3%) receiving spinal anesthesia without phenylephrine. There was no significant difference in the incidence of symptoms between groups receiving 7.5% glucose and those receiving 0.75% glucose (8.8% and 5% of patients, respectively).

Conclusions

These results suggest that adding phenylephrine to tetracaine for spinal anesthesia increases the potential for transient neurologic symptoms, but that the concentration of glucose does not affect their occurrence.
Determination of Plasma Concentrations of Propofol Associated with 50% Reduction in Postoperative Nausea
Authors: Gan T. J. , Glass P. S. A. , Howell S. T. , Canada A. T. , Grant A. P. , Ginsberg B.
Published: November 2003

Background

Subhypnotic doses of propofol possess direct antiemetic properties. The authors sought to determine the plasma concentration of propofol needed to effectively manage postoperative nausea and vomiting.

Methods

Patients aged 18-70 yr who were classified as American Society of Anesthesiologists physical status 1 or 2 and had surgery during general anesthesia were approached for the study. Only patients who had nausea (verbal rating score > 5 on a 0- to 10-point scale), retching, or vomiting in the postanesthetic care unit participated. Propofol was administered to these patients to achieve target plasma concentrations of 100, 200, 400, and 800 ng/ml using a computer-assisted continuous infusion device. Target concentrations were increased every 15 min until patients described at least a 50% reduction in symptoms on the verbal rating score. An arterial blood sample was obtained at each step. The measured plasma propofol concentrations were used to analyze data. Blood pressure, heart and respiratory rates, arterial blood saturation, sedation score, and overall satisfaction with treatment were recorded.

Results

Of the 89 patients who consented to the study, 15 patients met entry criteria and were enrolled. Five of these patients also had retching or vomiting when they entered the study. Fourteen patients responded successfully to treatment. One patient did not achieve the required response at plasma concentrations of 830 ng/ml. Hence the success rate for the treatment of postoperative nausea and vomiting was 93%. Among patients who responded, the median plasma concentration associated with an antiemetic response was 343 ng/ml. There was no difference in sedation scores from baseline and no episodes of desaturation. Hemodynamic parameters were stable during the study.

Conclusions

Propofol is generally efficacious in treating postoperative nausea and vomiting at plasma concentrations that do not produce increased sedation. Simulations indicate that to achieve antiemetic plasma propofol concentrations of 343 ng/ml, a bolus dose of 10 mg followed by an infusion of approximately 10 microg x kg(-1) x min(-1) are necessary.
Epidural Epinephrine and Clonidine
Authors: Curatolo Michele , Petersen-Felix Steen , Arendt-Nielsen Lars , Zbinden Alex M.
Published: November 2003

Background

It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues.

Methods

Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined.

Results

Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve.

Conclusions

Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.
Effects of Rapid Increases of Desflurane and Sevoflurane to Concentrations of 1.5 MAC on Systemic Vascular Resistance and Catecholamine Response during Cardiopulmonary Bypass
Authors: Rodig Gabriele , Keyl Cornelius , Kaluza Mirko , Kees Frieder , Hobbhahn Jonny
Published: November 2003

Background

Airway irritation was hypothesized to trigger the transient cardiovascular stimulation associated with desflurane. The authors administered desflurane during cardiopulmonary bypass (CPB), thus avoiding airway contact, and compared the effects of rapid increases of desflurane to 1.5 MAC on systemic vascular resistance index (SVRI) and catecholamine response to those of 1.5 MAC sevoflurane.

Methods

Forty-eight patients, undergoing elective coronary bypass surgery, were randomly allocated to receive either desflurane or sevoflurane during hypothermic (32-33 degrees C) nonpulsatile CPB at exhaust gas concentrations of 1.5 MAC for 15 min. SVRI was calculated at baseline, 1, 2, 3, 4, 5, 7, 9, 12, and 15 min after starting volatile anesthetics' delivery. Plasma catecholamine concentrations were determined in 12 desflurane-treated patients and 12 sevoflurane-treated patients at baseline, 5, and 15 min.

Results

The time-course of deltaSVRI, (changes in SVRI from baseline), from baseline to 5 min was significantly different between desflurane- and sevoflurane-treated patients, whereas there was no difference from 7 to 15 min. In the desflurane group, SVRI from 1 to 7 min remained unchanged to baseline level, thereafter declining to significantly lower values at 9, 12, and 15 min compared with values from 0 to 5 min, whereas sevoflurane produced an immediate and significant reduction in SVRI. With desflurane, catecholamine concentrations remained unchanged to baseline level at 5 and 15 min; with sevoflurane, they decreased with time.

Conclusions

The authors' results indicate that desflurane is associated with a different hemodynamic and catecholamine response compared with sevoflurane when administered into the oxygenator's gas supply line during CPB.
Bispectral Index Monitoring Allows Faster Emergence and Improved Recovery from Propofol, Alfentanil, and Nitrous Oxide Anesthesia
Authors: Gan Tong J. , Glass Peter S. , Windsor Alastair , Payne Fredrick , Rosow Carl , Sebel Peter , Manberg Paul
Published: November 2003

Background

The bispectral index (BIS), a parameter derived from the electroencephalograph (EEG), has been shown to correlate with increasing sedation and loss of consciousness. This study determined whether addition of BIS monitoring to standard anesthetic practice results in improvements in the conduct of anesthesia or in patient outcomes.

Methods

Three hundred two patients receiving a propofol-alfentanil-nitrous oxide anesthetic were studied at four institutions. Thirty-four patients were initially enrolled to determine preexisting anesthetic practice and patient outcomes at each institution. Subsequent patients were randomized to either standard clinical practice (SP group), or standard practice plus BIS monitoring (BIS group). In all patients, the anesthesiologist attempted to provide a stable anesthetic with the fastest possible recovery. BIS was recorded for all patients, but viewed only in the BIS group. In the BIS group, propofol infusions were adjusted to achieve a target BIS between 45-60, increasing to 60-75 during the final 15 min of the case. In the SP group, propofol dose adjustments were made based only on standard clinical signs. Drug use, intraoperative responses, and patient recovery parameters were recorded.

Results

Demographics were similar between groups. Compared with the SP group, patients in the BIS group required lower normalized propofol infusion rates (134 vs. 116 microg x kg[-1] x min[-1]; P < 0.001), were extubated sooner (11.22 vs. 7.25 min; P < 0.003), had a higher percentage of patients oriented on arrival to PACU (43% vs. 23%; P < 0.02), had better postanesthesia care unit (PACU) nursing assessments (P < 0.001), and became eligible for discharge sooner (37.77 vs. 31.70 min; P <0.04). There was no significant difference in the incidence of intraoperative responses between the groups.

Conclusions

Titrating propofol with BIS monitoring during balanced anesthesia decreased propofol use and significantly improved recovery. Intraoperative course was not changed. These findings indicate that the use of BIS may be valuable in guiding the administration of propofol intraoperatively.
Measurement of Cardiac Output by Pulse Dye Densitometry Using Indocyanine Green
Authors: Imai Takasuke , Takahashi Kenichirou , Fukura Haruhiko , Morishita Yasuo
Published: November 2003

Background

A new method for determining cardiac output (CO, l/min) using dye dilution combined with pulse dye densitometry (PDD), based on the principle of pulse oximetry, has been developed. The aim of the study was to determine the accuracy and precision of PDD by comparing it with the thermodilution method.

Methods

A prospective study was performed in 22 patients having surgery who were monitored using a pulmonary arterial catheter. In addition to the catheter, a specially designed photodetector was placed on the nasal wing. Ten milliliters of ice-cold indocyanine green dissolved in a 5% glucose solution (0.5 mg/ml) was injected. The dye and thermal dilution curves were simultaneously measured to calculate CO. Three to six injections were performed before and after surgery. Paired data were assessed in absolute terms, and the percentage errors were calculated by the degree of agreement and compared at three levels of CO (low < or = 3.5 < medium < or = 6 < high) by analysis of variance.

Results

The mean and SDs of the differences between dye and thermodilution CO were 0.16 +/- 0.80 l/min or 4.5 +/- 19.6% for 191 paired data. Measurement after surgery failed in one patient. The percentage error with low CO (9.3 +/- 19.3%) was greater (P < 0.05) than those obtained with other CO.

Conclusions

Pulse dye densitometry could measure CO repeatedly in patients having major surgery with the same degree of accuracy as the thermodilution method; however, a considerable degree of error was observed in some patients.
Factors Influencing the Tracheal Fluctuation of Inhaled Nitric Oxide in Patients with Acute Lung Injury
Authors: Umamaheswara Rao G. S. , Gallart Lluis , Law-Koune Jean-Dominique , Lu Qin , Puybasset Louis , Cluzel Philippe , Coriat Pierre , Rouby Jean-Jacques
Published: November 2003

Background

Inhaled nitric oxide (NO) improves arterial oxygenation in patients with acute lung injury (ALI) by selectively dilating pulmonary vessels perfusing ventilated lung areas. It can be hypothesized that NO uptake from the lung decreases with increasing ventilation perfusion mismatch. This study was undertaken to determine the factors influencing the fluctuation of tracheal NO concentration over the respiratory cycle as an index of NO pulmonary uptake in patients with ALI.

Methods

By using a prototype system (Opti-NO) delivering a constant flow of NO only during the inspiratory phase, 3 and 6 ppm of NO were administered during controlled mechanical ventilation into a lung model and to 11 patients with ALI. All patients had a thoracic computed tomography (CT) scan. Based on an analysis of tomographic densities, lungs were divided into three zones: normally aerated (-1.000 to -500 Hounsfield units [HU]), poorly aerated (-500 to -100 HU), and nonaerated (-100 to +100 HU), and the volume of each zone was computed. Concentrations of NO in the inspiratory limb and trachea were continuously measured by a fast-response chemiluminescence apparatus.

Results

In the lung model, tracheal NO concentration was stable with minor fluctuation. In contrast, in patients, tracheal NO concentration fluctuated widely during the respiratory cycle (55 +/- 10%). Because uptake of NO from the lungs was absent in the lung model but present in the patients, this fluctuation was considered as an index of pulmonary uptake of NO. This was further substantiated by (1) the coincidence of the peak and minimum tracheal NO concentration with the end-inspiratory and end-expiratory phases, respectively, and (2) continued decrease of tracheal NO concentration during prolonged expiratory phase. In patients with ALI, the fluctuation of tracheal NO concentration expressed as the difference between inspiratory and expiratory NO concentrations divided by inspiratory NO concentration was greater at 6 ppm than at 3 ppm (P < 0.01), was linearly correlated with normally aerated lung volume, inversely correlated with alveolar dead space and with poorly aerated lung volume.

Conclusion

In patients with ALI, fluctuation of tracheal NO concentration over the respiratory cycle can be considered as an index of NO uptake from the lungs that depends on aerated lung volume and perfusion of ventilated lung areas. At bedside, it may be used to follow the evolution of ventilation-perfusion mismatch.
Titration of Volatile Anesthetics Using Bispectral Index Facilitates Recovery after Ambulatory Anesthesia
Authors: Song Dajun , Joshi Girish P. , White Paul F.
Published: November 2003

Background

The bispectral (BIS) index has previously been shown to be a quantifiable measure of the sedative and hypnotic effects of anesthetic drugs. This study was designed to assess the effect of BIS monitoring on the utilization of volatile anesthetics and their recovery profiles after ambulatory surgery.

Methods

Sixty consenting women undergoing outpatient laparoscopic tubal ligation procedures were randomly assigned to one of four treatment groups. After a standardized induction, anesthesia was maintained with either desflurane (Groups I and II) or sevoflurane (Groups III and IV) in combination with nitrous oxide, 65%, and fentanyl. In the control groups (Groups I and III), the anesthesiologists were blinded to the BIS value, and the volatile anesthetics were administered according to standard clinical practice. In Groups II and IV, the volatile anesthetics were titrated to maintain the BIS value at 60. The volatile anesthetic usage and the times from discontinuation of anesthesia to verbal response, orientation, and home-readiness were recorded.

Results

During the maintenance period, the BIS values were significantly lower in the control groups (mean, 42) compared with the BIS-titrated groups (mean, 60). The volatile anesthetic usage in the BIS-titrated groups was 30-38% lower (P < 0.05) compared with the control groups. Similarly, the times to verbal responsiveness were 30-55% shorter in the BIS-titrated (vs. control) groups.

Conclusions

Titrating desflurane and sevoflurane using the BIS monitor decreased their utilization and contributed to a faster emergence from anesthesia in outpatients undergoing laparoscopic tubal ligation procedures.
Alfentanil Blocks Reflex Pupillary Dilation in Response to Noxious Stimulation But Does Not Diminish the Light Reflex
Authors: Larson Merlin D. , Kurz Andrea , Sessler Daniel I. , Dechert Martha , Bjorksten Andrew R. , Tayefeh Farzin
Published: November 2003

Background

Estimation of the mu-agonist opioid effect in anesthetized and paralyzed patients is often imprecise and can be obscured by concomitant administration of drugs that affect the sympathetic nervous system, such as beta-adrenergic blocking agents. As an alternative to hemodynamic measures of opioid effect, the authors tested the hypothesis that the pupillary light reflex or pupillary reflex dilation correlated with alfentanil concentrations during isoflurane anesthesia.

Methods

Six volunteers were anesthetized on 4 days with 0.8% isoflurane. Alfentanil was administered intravenously to target total plasma concentrations of 0, 25, 50, and 100 ng/ml. A 5-s tetanic electrical stimulus was applied to the skin. Pupil size and the pupillary light reflex were recorded before and after alfentanil administration, and before and for 8 min after the stimulus.

Results

Alfentanil exponentially impaired reflex pupillary dilation, decreasing the maximum response amplitude from 5 mm at 0 ng/ml, to 2.3 mm at 25 ng/ml, to 1.0 mm at 50 ng/ml, and finally to 0.2 mm at 100 ng/ml. In contrast, only the highest concentration of alfentanil depressed the dilation of the pupil in the first 2 s after the stimulus. Alfentanil administration had no effect on the pupillary light reflex.

Conclusions

Dilation of the pupil in response to a noxious stimulus is a measure of opioid effect in isoflurane-anesthetized volunteers. In contrast, the pupillary light reflex is unaffected by alfentanil during isoflurane anesthesia. These data suggest that stimulus-induced pupillary dilation may be used to evaluate the analgesic component of a combined volatile and opioid anesthetic.
Intrathecal Sufentanil for Labor Analgesia Does Not Cause a Sympathectomy
Authors: Riley Edward T. , Walker Dean , Hamilton Catherine L. , Cohen Sheila E.
Published: November 2003

Background

Intrathecal sufentanil (ITS) is frequently used to provide analgesia during labor. Decreases in blood pressure and sensory changes in this circumstance suggest that ITS may have a local anesthetic effect and thus cause a sympathectomy. To determine whether ITS given to laboring women causes a sympathectomy, the authors evaluated central and lower extremity temperature changes after ITS administration. These findings were compared with those in a control group of women having spinal anesthesia with bupivacaine for elective cesarean section in whom an extensive sympathectomy was expected.

Methods

Twenty parturients classified as American Society of Anesthesiologists' physical status 1 or 2 had temperatures measured centrally, at the calf, and at the great toe at frequent intervals after receiving 10 microg ITS for labor analgesia (sufentanil group, n = 10), or hyperbaric bupivacaine 12 mg in their spinal anesthetic for cesarean section (bupivacaine group, n = 10). Calf-to-toe temperature indices (C-T) were calculated by subtracting toe temperature from calf temperature. A decrease in this index means that the toe had warmed compared with the calf and is an indication of vasodilation and a sympathectomy.

Results

There was no significant change in the C-T indices or central temperature in the sufentanil group, but the C-T indices and central temperature decreased significantly in the bupivacaine group.

Conclusions

The decreases in the C-T index and central temperature in the bupivacaine group indicate the presence of a sympathectomy. The lack of change in the C-T indices and central temperature in the sufentanil group indicates that no significant vasodilation occurred. Therefore, the decrease in blood pressure seen after ITS administration for labor analgesia is unlikely to be the result of a sympathectomy.
Bupivacaine Inhibition of L-Type Calcium Current in Ventricular Cardiomyocytes of Hamster
Authors: Rossner Kenneth L. , Freese Kenneth J.
Published: November 2003

Background

The local anesthetic bupivacaine is cardiotoxic when accidentally injected into the circulation. Such cardiotoxicity might involve an inhibition of cardiac L-type Ca2+ current (ICa,L). This study was designed to define the mechanism of bupivacaine inhibition of ICa,L.

Methods

Cardiomyocytes were enzymatically dispersed from hamster ventricles. Certain voltage- and time-dependencies of ICa,L were recorded using the whole-cell patch clamp method in the presence and absence of different concentrations of bupivacaine.

Results

Bupivacaine, in a concentration-dependent manner (10-300 microM), tonically inhibited the peak amplitude of ICa,L. The inhibition was characterized by an increase in the time of recovery from inactivation and a negative-voltage shift of the steady-state inactivation curve. The inhibition was shown to be voltage-dependent, and the peak amplitude of ICa,L could not be restored to control levels by a wash from bupivacaine.

Conclusions

The inhibition of ICa,L appears, in part, to result from bupivacaine predisposing L-type Ca channels to the inactivated state. Data from washout suggest that there may be two mechanisms of inhibition at work. Bupivacaine may bind with low affinity to the Ca channel and also affect an unidentified metabolic component that modulates Ca channel function.
Effect of Midazolam on Propofol-induced Positive Affective State Assessed by Place Conditioning in Rats
Authors: Pain Laure , Oberling Philippe , Sandner Guy , Di Scala Georges
Published: November 2003

Background

The effect of either midazolam or the combination of midazolam and propofol on the affective state was assessed in rats at subanesthetic doses and at recovery from anesthesia.

Methods

The putative drug(s)-induced affective states were repeatedly paired with one of two distinguishable compartments of an experimental cage, whereas the vehicle(s)-induced effect was repeatedly paired with the other compartment. During a subsequent choice test for one compartment over the other, the rats' preference for the drug(s)-paired compartment over the vehicle(s)-paired compartment is indicative of a pleasant state induced by the drug(s). In experiment 1, rats were conditioned with different doses of midazolam either at subanesthetic states or at recovery from anesthesia. In experiment 2, groups of rats were conditioned with different combinations of midazolam and propofol either at subanesthetic states or at recovery from anesthesia induced jointly by midazolam (10 mg/kg) and propofol (60 mg/kg). Experiment 3 was conducted in the same way as experiment 2, except that midazolam was paired with both compartments. In addition, these groups were tested not only in an undrugged state but also in a drugged (with midazolam) state.

Results

In experiment 1, rats exhibited a place preference for the environment previously associated with midazolam, at subanesthetic and anesthetic doses. Experiment 2 showed that a propofol-induced place preference was found to be dose-dependently suppressed by midazolam. Experiment 3 replicated the findings of experiment 2 and extended them to the mechanism by which midazolam blocked a propofol-induced place preference.

Conclusions

Midazolam administered before propofol blocked the expression of a propofol-induced pleasant state.
Cost-effective Reduction of Neuromuscular-blocking Drug Expenditures
Authors: Freund Peter R. , Bowdle T. Andrew , Posner Karen L. , Kharasch Evan D. , Burkhart V. dePaul
Published: November 2003

Background

Anesthetic drug expenditures have been a focus of cost-containment efforts. The aim of this study was to determine whether expenditures for neuromuscular-blocking agents could be reduced without compromising outcome, and to determine whether such a cost-effective pattern of neuromuscular blocker use could be sustained.

Methods

Education, practice guidelines, and paperwork barriers were used to persuade anesthesiologists to substitute low-cost neuromuscular-blocking drugs (pancuronium or a metocurine-pancuronium combination) for a more costly neuromuscular-blocking drug (vecuronium). Neuromuscular-blocking drug use in all patients during a historical control period (6 months; n = 4,804) was compared with that during two consecutive 1-yr periods of intervention (n = 9,761/n = 10,695). Expenditures for vecuronium and for all neuromuscular-blocking drugs were compared for the control and intervention periods. The rate of complications related to neuromuscular-blocking drugs was determined by an ongoing continuous quality improvement program.

Results

Vecuronium use decreased by 76% during the first and second yr of intervention, compared with the historical period (P < 0.01). The cost of neuromuscular-blocking drugs decreased by 31% (P < 0.01) and 47% (P < 0.01) for the first and second yr, respectively. The complication rate related to neuromuscular-blocking drugs was 0.081% in the historical period and 0.11% and 0.093% during the intervention periods (P = 0.29 and 0.41).

Conclusion

Practice guidelines, education, and paperwork barriers used together substantially reduced the expenditures for neuromuscular-blocking drugs for 2 yr without adversely affecting clinical outcome.
Spinal Anesthesia Speeds Active Postoperative Rewarming
Authors: Szmuk Peter , Ezri Tiberiu , Sessler Daniel I. , Stein Arnold , Geva Daniel
Published: November 2003

Background

Redistribution of body heat decreases core temperature more during general than regional anesthesia. However, the combination of anesthetic- and sedative-induced inhibition may prevent effective upper-body thermoregulatory responses even during regional anesthesia. The extent to which each type of anesthesia promotes hypothermia thus remains controversial. Accordingly, the authors evaluated intraoperative core hypothermia in patients assigned to receive spinal or general anesthesia. They also tested the hypothesis that the efficacy of active postoperative warming is augmented when spinal anesthesia maintains vasodilation.

Methods

Patients undergoing lower abdominal and leg surgery were randomly assigned to receive general anesthesia (isoflurane and nitrous oxide; n = 20) or spinal anesthesia (bupivacaine; n = 20). Fluids were warmed to 37 degrees C and patients were covered with surgical drapes. However, no other active warming was applied during operation. Ambient temperatures were maintained near 20 degrees C. After operation, patients were warmed with a full-length, forced-air cover set to 43 degrees C. Shivering, when observed, was treated with intravenous meperidine.

Results

The mean spinal analgesia level, which was at the sixth thoracic level during surgery, remained at the T12 dermatome after 90 min after operation. Core temperatures did not differ significantly during surgery and decreased to 34.4 +/- 0.5 degrees C and 34.1 +/- 0.4 degrees C, respectively, in patients given spinal and general anesthesia. After operation, however, core temperatures increased significantly faster (1.2 +/- 0.1 degrees C/h vs. 0.7 +/- 0.2 degrees C/h, mean +/- SD; P < 0.001) in patients given spinal anesthesia. Consequently, patients given spinal anesthesia required less time to rewarm to 36.5 degrees C (122 +/- 28 min vs. 199 +/- 28 min; P < 0.001).

Conclusions

Comparable intraoperative hypothermia during general and regional anesthesia presumably resulted because the combination of spinal anesthesia and meperidine administration obliterated effective peripheral and central thermoregulatory control. Vasodilation increased the rate of core rewarming in patients after operation with residual lower-body sympathetic blocks, suggesting that vasoconstriction decreased peripheral-to-core heat transfer after general anesthesia.
Cerebral Emboli during Cardiac Surgery in Children
Authors: O'Brien James J. , Butterworth John , Hammon John W. , Morris Kristin J. , Phipps Julia M. , Stump David A.
Published: November 2003

Background

Microemboli occur commonly during cardiac surgery in adults, and, when present, increase the risk of neuropsychological deficits. Their incidence and significance during correction of congenital heart disease is unknown. The authors hypothesized that microemboli would occur before bypass with right-to-left cardiac shunts and would also occur in large numbers when the aortic crossclamp was released in children during repair of congenital heart defects.

Methods

In 25 children studied with carotid artery Doppler, embolic signals were counted and timed in relation to 13 intraoperative events. Patients were classified as either at high risk (obligate right-to-left shunt or uncorrected transposition of the great arteries) or at low risk (net left-to-right shunt or simple obstructive lesions) for paradoxical (venous to arterial) emboli.

Results

The median number of emboli detected was 122 (range, 2-2,664). Forty-two percent of all emboli were detected within 3 min of release of the aortic crossclamp. The high-risk group had significantly more emboli (median, 66; range, 0-116) during the time interval before cardiopulmonary bypass than did the low-risk group (median, 8; range, 0-73), with P < 0.01. There was no significant difference between the high- and low-risk groups in the total number of emboli detected. There was no apparent association between number of emboli and gross neurologic deficits.

Conclusions

Microemboli can be detected in the carotid arteries of children undergoing repair of congenital heart disease and are especially prevalent immediately after release of the aortic crossclamp. The role of emboli in causing neurologic injury in children undergoing repair of congenital heart disease remains to be determined.
Opioid-sparing Effects of a Low-dose Infusion of Naloxone in Patient-administered Morphine Sulfate
Authors: Gan Tong J. , Ginsberg Brian , Glass Peter S. A. , Fortney Jennifer , Jhaveri Rajiv , Perno Rhonda
Published: November 2003

Background

A naloxone infusion is effective in reducing epidural and intrathecal opioid-related side effects. The use of naloxone infusion concomitant with intravenous morphine patient-controlled analgesia (PCA) has not been evaluated, probably because of an expected direct antagonism of the systemic opioid effect. The authors compared the incidence of morphine-related side effects and the quality of analgesia from two small doses of naloxone infusion.

Methods

Sixty patients classified as American Society of Anesthesiologists physical status 1, 2, or 3 who were scheduled for total abdominal hysterectomies were enrolled in the study. Patients received a standardized general anesthetic. In the postanesthetic care unit, patients received morphine as a PCA. They were randomized to receive either 0.25 microg x kg(-1) x h(-1) naloxone (low dose), 1 microg x kg(-1) x h(-1) (high dose), or saline (placebo) as a continuous infusion. Verbal rating scores for pain, nausea, vomiting, and pruritus; sedation scores; requests for antiemetic; and morphine use were recorded for 24 h. Blood pressure, respiratory rate, and oxyhemoglobin saturation were also monitored.

Results

Sixty patients completed the study. Both naloxone doses were equally effective in reducing the incidence of nausea, vomiting, and pruritus compared with placebo (P < 0.05 by the chi-squared test). There was no difference in the verbal rating scores for pain between the groups. The cumulative morphine use was the lowest in the low-dose group (42.3 +/- 24.1 mg; means +/- SD) compared with the placebo (59.1 +/- 27.4 mg) and high-dose groups (64.7 +/- 33.0 mg) at 24 h (P < 0.05 by analysis of variance). There was no incidence of respiratory depression (<8 breaths/min) and no difference in sedation scores, antiemetic use, respiratory rate, and hemodynamic parameters among the groups.

Conclusions

Naloxone is effective in preventing PCA opioid-related side effects. Naloxone infusion at 0.25 microg x kg(-1) x h(-1) not only attenuates these side effects but appears to reduce postoperative (beyond 4-8 h) opioid requirements. This dosing regimen can be prepared with 400 microg naloxone in 1,000 ml crystalloid given in 24 h to a patient weighing 70 kg.
Midazolam Changes Cerebral Blood Flow in Discrete Brain Regions
Authors: Veselis Robert A. , Reinsel Ruth A. , Beattie Bradley J. , Mawlawi Osama R. , Feshchenko Vladimir A. , DiResta Gene R. , Larson Steven M. , Blasberg Ronald G.
Published: November 2003

Background

Changes in regional cerebral blood flow (rCBF) determined with H2(15)O positron emission tomographic imaging can identify neural circuits affected by centrally acting drugs.

Methods

Fourteen volunteers received one of two midazolam infusions adjusted according to electroencephalographic response. Low or high midazolam effects were identified using post-hoc spectral analysis of the electroencephalographic response obtained during positron emission tomographic imaging based on the absence or presence of 14-Hz spindle activity. The absolute change in global CBF was calculated, and relative changes in rCBF were determined using statistical parametric mapping with localization to standard stereotactic coordinates.

Results

The low-effect group received 7.5 +/- 1.7 mg midazolam (serum concentrations, 74 +/- 24 ng/ml), and the high-effect group received 9.7 +/- 1.3 mg midazolam (serum concentrations, 129 +/- 48 ng/ml). Midazolam decreased global CBF by 12% from 39.2 +/- 4.1 to 34.4 +/- 6.1 ml x 100 g(-1) x min(-1) (P < 0.02 at a partial pressure of carbon dioxide of 40 mmHg). The rCBF changes in the low-effect group were a subset of the high-effect group. Decreased rCBF (P < 0.001) occurred in the insula, the cingulate gyrus, multiple areas in the prefrontal cortex, the thalamus, and parietal and temporal association areas. Asymmetric changes occurred, particularly in the low-effect group, and were more significant in the left frontal cortex and thalamus and the right insula. Relative rCBF was increased in the occipital areas.

Conclusion

Midazolam causes dose-related changes in rCBF in brain regions associated with the normal functioning of arousal, attention, and memory.
Opioid Effects on Mitogen-activated Protein Kinase Signaling Cascades
Authors: Gutstein Howard B. , Rubie Elizabeth A. , Mansour Alfred , Akil Huda , Woodgett James R.
Published: November 2003

Background

The molecular mechanisms underlying both beneficial and undesirable opioid actions are poorly understood. Recently, the three currently known mammalian mitogen-activated protein kinase (MAPK) signaling cascades (extracellular signal-related kinase [ERK], stress-activated protein kinase, and p38 kinase) were shown to play important roles in transducing receptor-mediated signaling processes.

Methods

To determine whether any of these kinase cascades were activated by opioids, mu, delta, or kappa opioid receptors were transiently introduced into COS-7 cells together with MAPKs tagged to allow recognition by specific antibodies, and then exposed to opioids. Mitogen-activated protein kinase activation was determined by an in vitro MAPK activation assay. In addition, C6 glioma cells with either mu, delta, or kappa receptors stably introduced were exposed to opioids and MAPK activation determined by in vitro activation assay or antibody detection of activated forms.

Results

Transient experiments in COS cells revealed potent stimulation of ERK by mu and delta receptor activation, weak stimulation of stress-activated protein kinase by all receptor types, and no activation of p38. In stably transfected C6 glioma cells, only ERK activation was observed. Extracellular signal-related kinase induction was rapid, peaking 5 min after stimulation, and its activation was receptor-type specific. Mu and delta receptor stimulation activated ERK, but kappa stimulation did not.

Conclusions

These results show that acute opioid signaling is not only inhibitory, but can strongly activate an important signaling cascade. Extracellular signal-related kinase activation may contribute to desirable responses to opioids, such as analgesia and sedation, and also to undesirable adaptive responses, such as tolerance, physical dependence, and possibly addiction. Further study of this system could provide greater insight into the molecular mechanisms underlying these clinical problems.
Comparison of the Effects of Propofol and Pentobarbital on Neurologic Outcome and Cerebral Infarct Size after Temporary Focal Ischemia in the Rat
Authors: Pittman Janet E. , Sheng Huaxin , Pearlstein Robert , Brinkhouse Ann , Dexter Franklin , Warner David S.
Published: November 2003

Background

Although propofol is known to have effects on cerebral physiology similar to the barbiturates, a direct comparison of the relative effects of these drugs on outcome from cerebral ischemia has not been performed. The authors postulated that pentobarbital or propofol would yield similar effects on neurologic and histologic outcome from temporary focal ischemia in the rat.

Methods

Wistar rats were anesthetized with sufficient doses of pentobarbital (n = 20) or propofol (n = 20) to cause electroencephalographic burst suppression. The middle cerebral artery was then occluded for 75 min. Animals were awakened 4-6 h after onset of reperfusion and allowed to recover for 1 week. Neurologic function and infarct size were then assessed.

Results

Relevant physiologic values were similar between groups during ischemia and early reperfusion. No difference between groups was observed for severity of hemiparesis (P = 0.10). Total cerebral infarct volumes (median +/- quartile deviation) were similar for the two groups (pentobarbital = 190 +/- 36 mm3; propofol = 200 +/- 24 mm3, P = 0.35).

Conclusion

Neurologic and histologic outcome were similar in pentobarbital or propofol anesthetized rats undergoing temporary focal cerebral ischemia and a 1-week recovery interval.
Atelectasis Is a Major Cause of Hypoxemia and Shunt after Cardiopulmonary Bypass
Authors: Magnusson Lennart , Zemgulis Vitas , Wicky Stephan , Tyden Hans , Thelin Stefan , Hedenstierna Goran
Published: November 2003

Background

Respiratory failure after cardiopulmonary bypass (CPB) remains a major complication after cardiac surgery. The authors tested the hypothesis that atelectasis is an important factor responsible for the increase in intrapulmonary shunt after CPB.

Methods

Six pigs received standard CPB (bypass group). Six other pigs had the same surgery but without CPB (sternotomy group). Another six pigs were anesthetized for the same duration but without any surgery (control group). The ventilation-perfusion distribution was measured with the inert gases technique, extravascular lung water was quantified by the double-indicator distribution technique, and atelectasis was analyzed by computed tomography.

Results

Intrapulmonary shunt increased markedly after bypass but was unchanged over time in the control group (17.9 +/- 6.2% vs. 3.5 +/- 1.2%; P < 0.0001). Shunt also increased in the sternotomy group (10 +/- 2.6%; P < 0.01 compared with baseline) but was significantly lower than in the bypass group (P < 0.01). Extravascular lung water was not significantly altered in any group. The pigs in the bypass group showed extensive atelectasis (32.3 +/- 28.7%), which was significantly larger than in the two other groups. The pigs in the sternotomy group showed less atelectasis (4.1 +/- 1.9%) but still more (P < 0.05) than the controls (1.1 +/- 1.6%). There was good correlation between shunt and atelectasis when all data were pooled (R2 = 0.67; P < 0.0001).

Conclusions

Atelectasis is produced to a much larger extent after CPB than after anesthesia alone or with sternotomy and it explains most of the marked post-CPB increase in shunt and hypoxemia. Surgery per se contributes to a lesser extent to postoperative atelectasis and gas exchange impairment.
Riluzole Blocks Dopamine Release Evoked by N-methyl-D-aspartate, Kainate, and Veratridine in the Rat Striatum
Authors: Keita Hawa , Lepouse Claire , Henzel Danielle , Desmonts Jean-Marie , Mantz Jean
Published: November 2003

Background

Dopamine (DA) is released in large amounts during cerebral ischemia and may exacerbate tissue damage. Riluzole (54274 RP) is a recently developed agent that depresses glutamate neurotransmission in the central nervous system (CNS) and that may protect against ischemic injury in some animal models. Because glutamate stimulates the release of DA in the striatum, the authors hypothesized that riluzole could antagonize DA release in this structure.

Methods

Assay for DA release consisted of superfusing 3H-DA preloaded synaptosomes with artificial cerebrospinal fluid (1 ml/min, 37 degrees C) and measuring the radioactivity obtained from 1-min fractions over 22 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with riluzole (0.1-100 microM, 5 min), and finally with no pharmacologic stimulation (9 min). The following depolarizing agents were tested: KCl (9, 15 mM), veratridine (0.01-1 microM), N-methyl-D-aspartate (NMDA, 0.1-1 mM), kainate (0.1-1 mM), and nicotine (0.01-0.5 mM). Assay for DA uptake was performed by measuring the radioactivity incorporated in synaptosomes incubated with 3H-DA (44 nM; 5 min; 37 degrees C).

Results

All depolarizing agents produced a significant, concentration-related increase from basal 3H-DA release. Riluzole was found to decrease the release induced by veratridine (1 microM), NMDA (1 mM), and kainate (1 mM) in a significant, concentration-related manner (IC50 = 9.5 microM, 1.6 microM, and 5.8 microM for veratridine, NMDA, and kainate, respectively). In contrast, it did not affect the release elicited by either KCl or nicotine. Riluzole had no significant effect on the specific 3H-DA uptake.

Conclusions

Riluzole produced a potent blockade of the release of DA mediated by activation of presynaptic sodium channels, NMDA, and kainate receptors. Depression of glutamate transmission together with blockade of DA release may contribute to the actions of this agent in vivo.