bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionic Basis of the Differential Effects of Intravenous Anesthetics on Erythromycin-induced Prolongation of Ventricular Repolarization in the Guinea Pig Heart
Authors: Morey Timothy E. , Martynyuk Anatoly E. , Napolitano Charles A. , Raatikainen M. J. Pekka , Guyton Thomas S. , Dennis Donn M.
Published: November 2003

Background

Dysrhythmias and death occur in patients with acquired long QT syndrome (LQTS). Little information exists regarding interactions between anesthetics and drugs that prolong ventricular repolarization. Therefore the effects of three commonly used intravenous anesthetics on ventricular repolarization were investigated in the setting of drug-induced, long QT syndrome.

Methods

The effects of increasing concentrations (0, 10, 25, and 50 microM) of propofol, ketamine, and thiopental on ventricular repolarization were evaluated by measuring the monophasic action potential duration at 90% repolarization (MAPD90) in guinea pig Langendorff-perfused hearts in the absence or presence of erythromycin (100 microM). If an anesthetic enhanced erythromycin-induced prolongation of MAPD90, its effects on the delayed rectifier (I[K]) and inward rectifier (I[Kl]) potassium currents were measured using the whole-cell patch-clamp technique.

Results

At clinically relevant concentrations, only thiopental significantly modulated erythromycin's effect on MAPD90. Thiopental at 10, 25, and 50 microM prolonged MAPD90 from a control of 163 +/- 6 ms by 18 +/- 4, 30 +/- 3, and 31 +/- 4 ms, respectively. In a separate group, erythromycin prolonged MAPD90 from 155 +/- 2 ms to 171 +/- 2 ms (n = 21, P < 0.001). In the presence of erythromycin, thiopental at 10, 25, and 50 microM caused significantly greater prolongation from a control of 171 +/- 2 ms by 39 +/- 2, 58 +/- 3, and 72 +/- 6 ms, respectively. Whole-cell patch-clamp experiments indicated that thiopental inhibited I(K) and I(Kl).

Conclusions

Intravenous anesthetics caused markedly different effects on ventricular repolarization. Thiopental, unlike propofol and ketamine, potentiated the effects of erythromycin on ventricular repolarization by inhibiting I(K) and I(Kl).
The Intubation Difficulty Scale (IDS)
Authors: Adnet Frederic , Borron Stephen W. , Racine Stephane X. , Clemessy Jean-Luc , Fournier Jean-Luc , Plaisance Patrick , Lapandry Claude
Published: November 2003

Background

A quantitative scale of intubation difficulty would be useful for objectively comparing the complexity of endotracheal intubations. The authors have developed a quantitative score that can be used to evaluate intubating conditions and techniques with the aim of determining the relative values of predictive factors of intubation difficulty and of the techniques used to decrease such difficulties.

Methods

An Intubation Difficulty Scale (IDS) was developed, based on parameters known to be associated with difficult intubation. It was then evaluated prospectively in a group of 311 consecutive prehospital intubations and 315 intubations in an operating room. In the operating room, the IDS was compared with two other parameters: the time to completion of intubation and the visual analog scale (VAS). Time was measured by an independent observer. Operators in both groups completed a checklist regarding the conditions of intubation.

Results

There is a good correlation between the IDS scale and the VAS assessment of difficulty and time to completion of intubation. VAS and time to completion have a significant but lesser correlation to each other. Comparison of IDS with operator-assessed subjective categorical impression of difficulty by Kruskall-Wallis was statistically significant.

Conclusions

The IDS correlates with but is less subjective than the VAS and categorical classification. IDS correlates with time to intubation, but it offers details regarding the difficulty encountered that time alone does not. This score may not only aid in evaluation of factors linked to difficult intubations, but it may provide a uniform approach to comparing studies related to this subject.
Greater Incidence of Delirium during Recovery from Sevoflurane Anesthesia in Preschool Boys
Authors: Aono Jun , Ueda Wasa , Mamiya Kikyo , Takimoto Eri , Manabe Masanobu
Published: November 2003

Background

In the authors' clinical experience, preschool children are more likely to show delirium after sevoflurane than are older children.

Methods

Sixty-three preschool boys aged 3-5 yr (classified as American Society of Anesthesiologists [ASA] physical status I), and 53 school-age boys aged 6-10 yr (ASA physical status I) who underwent minor urologic surgery were randomly assigned to receive either halothane or sevoflurane, thus creating four groups: preschool-halothane (n = 32), preschool-sevoflurane (n = 31), school-halothane (n = 27), and school-sevoflurane (n = 26). Anesthesia was induced by inhalation of halothane or sevoflurane in oxygen and was maintained at 1 minimum alveolar concentration of each agent throughout surgery. For intra- and postoperative analgesia, caudal block with 0.5-1.0 ml/kg 0.25% plain bupivacaine and topical infiltration with 3-5 ml 1% lidocaine were provided for all patients. Recovery characteristics and incidence of delirium on emergence were compared among the four groups.

Results

Two patients in the preschool-halothane group, one in the preschool-sevoflurane group, and one in the school-halothane group were excluded from the comparison because of insufficient analgesia or agitation before induction. In both age groups, the time to emergence from sevoflurane was significantly faster (about 3 min) than from halothane. The incidence of delirium during recovery in the preschool-sevoflurane group (40%) was significantly greater than that in the other groups (preschool-halothane, 10%; school-halothane, 15.4%; school-sevoflurane, 11.5%).

Conclusion

Sevoflurane provided quicker emergence and early recovery compared with halothane, but the incidence of delirium was greater in preschool boys after sevoflurane.
Mild Intraoperative Hypothermia Prolongs Postanesthetic Recovery
Authors: Lenhardt Rainer , Marker Elvine , Goll Veronika , Tschernich Heinz , Kurz Andrea , Sessler Daniel I. , Narzt Edith , Lackner Franz
Published: November 2003

Background

Intraoperative hypothermia is common and persists for several hours after surgery. Hypothermia may prolong immediate recovery by augmenting anesthetic potency, delaying drug metabolism, producing hemodynamic instability, or depressing cognitive function. Accordingly, the authors tested the hypothesis that intraoperative hypothermia prolongs postoperative recovery.

Methods

Patients undergoing elective major abdominal surgery (n = 150) were anesthetized with isoflurane, nitrous oxide, and fentanyl. They were randomly assigned to routine thermal management (hypothermia) or extra warming (normothermia). Postoperative surgical pain was treated with patient-controlled analgesia. Fitness for discharge from the postanesthesia care unit was evaluated at 20-min intervals by investigators blinded to group assignment and postoperative core temperatures. Scoring was based on a modification of a previously published system that included activity, ventilation, consciousness, and hemodynamic responses. Patients were considered fit for discharge when they sustained a score of 80% (13 points) for at least two consecutive measurement periods.

Results

Morphometric characteristics and anesthetic management were similar in each group. Final intraoperative core temperatures differed by approximately 2 degrees C: 34.8 +/- 0.6 versus 36.7 +/- 0.6 degrees C (mean +/- SD, P < 0.001). Postoperative pain scores and postoperative use of patient-controlled opioid were similar. Hypothermic patients required approximately 40 min longer (94 +/- 65 vs. 53 +/- 36 min) to reach fitness for discharge, even when return to normothermia was not a criterion (P < 0.001). Duration of recovery in the two groups differed by approximately 90 min when a core temperature >36 degrees C was also required (P < 0.001).

Conclusion

Maintaining core normothermia decreases the duration of postanesthetic recovery and may, therefore, reduce costs of care.
Comparison of the Bullard and Macintosh Laryngoscopes for Endotracheal Intubation of Patients with a Potential Cervical Spine Injury
Authors: Watts Andrew D. J. , Gelb Adrian W. , Bach David B. , Pelz David M.
Published: November 2003

Background

In the emergency trauma situation, in-line stabilization (ILS) of the cervical spine is used to reduce head and neck extension during laryngoscopy. The Bullard laryngoscope may result in less cervical spine movement than the Macintosh laryngoscope. The aim of this study was to compare cervical spine extension (measured radiographically) and time to intubation with the Bullard and Macintosh laryngoscopes during a simulated emergency with cervical spine precautions taken.

Methods

Twenty-nine patients requiring general anesthesia and endotracheal intubation were studied. Patients were placed on a rigid board and anesthesia was induced. Laryngoscopy was performed on four occasions: with the Bullard and Macintosh laryngoscopes both with and without manual ILS. Cricoid pressure was applied with ILS. To determine cervical spine extension, radiographs were exposed before and during laryngoscopy. Times to intubation and grade view of the larynx were also compared.

Results

Cervical spine extension (occiput-C5) was greatest with the Macintosh laryngoscope (25.9 degrees +/- 2.8 degrees). Extension was reduced when using the Macintosh laryngoscope with ILS (12.9 +/- 2.1 degrees) and the Bullard laryngoscope without stabilization (12.6 +/- 1.8 degrees; P < 0.05). Times to intubation were similar for the Macintosh laryngoscope with ILS (20.3 +/- 12.8 s) and for the Bullard without ILS (25.6 +/- 10.4 s). Manual ILS with the Bullard laryngoscope results in further reduction in cervical spine extension (5.6 +/- 1.5 degrees) but prolongs time to intubation (40.3 +/- 19.5 s; P < 0.05).

Conclusions

Cervical spine extension and time to intubation are similar for the Macintosh laryngoscope with ILS and the Bullard laryngoscope without ILS. However, time to intubation is significantly prolonged when the Bullard laryngoscope is used in a simulated emergency with cervical spine precautions taken. This suggests that the Bullard laryngoscope may be a useful adjunct to intubation of patients with potential cervical spine injury when time to intubation is not critical.
Lack of Analgesic Activity of Morphine-6-glucuronide after Short-term Intravenous Administration in Healthy Volunteers
Authors: Lotsch Jorn , Kobal Gerd , Stockmann Anne , Brune Kay , Geisslinger Gerd
Published: November 2003

Background

The analgesic activity of morphine-6-glucuronide (M-6-G) is well recognized for its contribution to the effects of morphine and its possible use as an opioid analgesic with a wider therapeutic range than morphine. The present study attempted to quantify the relative contribution of M-6-G to analgesia observed after systemic administration of morphine.

Methods

In a placebo-controlled, sixfold crossover study in 20 healthy men, the effects of M-6-G were assessed at steady-state plasma concentrations of M-6-G identical to and two and three times higher than those measured after administration of morphine. Morphine and M-6-G were administered as an intravenous bolus followed by infusion over 4 h. Dosage A was M-6-G-bolus of 0.015 mg/kg plus infusion of 0.0072 mg x kg(-1) x h(-1). Dosage B was M-6-G-bolus of 0.029 mg/kg plus infusion of 0.014 mg x kg(-1) x h(-1). Dosage C was M-6-G-bolus of 0.044 mg/kg plus infusion of 0.022 mg x kg(-1) x h(-1). Dosage D was a morphine bolus of 0.14 mg/kg plus infusion of 0.05 mg x kg(-1) x h(-1) for 4 h. Dosage E was M-6-G combined with morphine (doses A + D). Dosage F was a placebo. The analgesic effects of M-6-G and morphine were measured before administration of the bolus and after 3.5 h using an experimental pain model based on pain-related cortical potentials and pain ratings after specific stimulation of the nasal nociceptor with short pulses of gaseous carbon dioxide.

Results

Morphine significantly reduced subjective and objective pain correlates compared with placebo. In contrast, M-6-G produced no statistically significant effects. The addition of M-6-G to morphine did not increase the effects of morphine. Morphine produced significantly more side effects than M-6-G.

Conclusion

After short-term intravenous administration at doses that produce plasma concentrations of M-6-G similar to those seen after administration of morphine, M-6-G had no analgesic effects in the present placebo-controlled study in healthy volunteers.
Sympathovagal Effects of Spinal Anesthesia Assessed by the Spontaneous Cardiac Baroreflex
Authors: Gratadour P. , Viale J. P. , Parlow J. , Sagnard P. , Counioux H. , Bagou G. , Annat G. , Hughson R. , Quintin L.
Published: November 2003

Background

The changes in sympathovagal balance induced by spinal anesthesia remain controversial. The spontaneous baroreflex method allows the continuous assessment of the spontaneous engagement of the cardiac baroreflex, giving an index of sympathovagal balance. The purpose of this study was to follow the effects of spinal anesthesia on spontaneous baroreflex sensitivity.

Methods

Continuous electrocardiogram and noninvasive blood pressure were recorded in 24 patients scheduled for elective inguinal hernia repair and randomly assigned to three groups: (1) no volume loading, (2) volume loading of 15 ml/kg lactated Ringer's solution, and (3) continuous infusion of etilefrine (an ephedrine-like drug). Each patient was studied before, during, and after bupivacaine-induced spinal anesthesia (mean sensory block: T4). Spontaneous baroreflex sensitivity and parameters of time-domain analysis of heart rate variability were calculated from 30 min of recording of each period.

Results

No significant change in spontaneous baroreflex slope or parameters of time-domain analysis were observed after regional anesthesia in any group. However, three patients experienced episodes of bradycardia and hypotension in the absence of a high block; these three patients showed an increase in spontaneous baroreflex sensitivity and time-domain parameters.

Conclusions

Using a noninvasive, continuous technique to estimate cardiac sympathovagal balance, no significant variation in autonomic balance induced by spinal anesthesia was observed. However, untoward episodes of bradycardia and hypotension occurred in three patients, who could not be prospectively identified by the parameters studied.
Dose-Response of Rocuronium Bromide in Children Anesthetized with Propofol
Authors: Woolf Rex L. , Crawford Mark W. , Choo Shu May
Published: November 2003

Background

The aim of this study was to determine the potency of rocuronium during propofol/fentanyl/N2O anesthesia in children and to compare the time course of action of rocuronium at doses of two and three times the ED95 with that of succinylcholine.

Methods

Rocuronium (120, 160, 200, or 240 microg/kg) was administered to 48 children aged 2-10 yr. Neuromuscular block was assessed by monitoring the electromyographic response of the adductor digiti minimi to supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s every 10 s. Potency was determined by log-probit transformation and least-squares linear regression analysis of dose and response. In a second group of 30 children, the onset and recovery profile of rocuronium at doses of two and three times the ED95 was compared with that of succinylcholine (2 mg/kg).

Results

Values for ED50 and ED95 were 210 +/- 24 and 404 +/- 135 microg/kg, respectively. The time to 90% neuromuscular block after 1.2 mg/kg rocuronium (three times the ED95), 33 +/- 5 s (mean +/- SD), did not differ significantly from that after succinylcholine, at 30 +/- 7 s; however, both were significantly less than that after 0.8 mg/kg rocuronium, 46 +/- 8 s (P < 0.05). The time to 25% recovery from 1.2 microg/kg rocuronium, 41 +/- 13 min, was approximately 50% greater than that after 0.8 mg/kg, at 27 +/- 6 min (P < 0.001), and eight times greater than that after succinylcholine, at 5.2 +/- 1.9 min (P < 0.001).

Conclusions

Both 1.2 mg/kg rocuronium (three times the ED95) and 2 mg/kg succinylcholine provide 90% neuromuscular block within 45 s in 95% of children. The present dose-response data support the use of rocuronium at a dose of 1.2 mg/kg when rapid onset and intermediate-duration neuromuscular block are needed in children.
Emulsion Formulation Reduces Propofol's Dose Requirements and Enhances Safety
Authors: Dutta Sandeep , Ebling William F.
Published: November 2003

Background

Propofol, a highly lipophilic anesthetic, is formulated in a lipid emulsion for intravenous use. Propofol has brisk onset and offset of effect after rapid administration and retains rapid offset characteristics after long-term administration. The authors tried to determine whether the emulsion vehicle is requisite for propofol's evanescent effect-time profile.

Methods

The time course of sedation and electroencephalographic (EEG) effect after propofol administration was measured in three studies in rats instrumented. In study 1, propofol was infused in either emulsion or lipid-free vehicle (n = 12), in a repeated measures cross-over design. In study 2, propofol in lipid-free vehicle was infused with or without simultaneous infusion of drug-free lipid emulsion (n = 6) in a repeated measures cross-over design. In study 3, propofol was infused in either emulsion (n = 5) or lipid-free vehicle (n = 5) to EEG burst suppression.

Results

In study 1, relative to the emulsion formulation, propofol administered at equivalent doses in lipid-free vehicle resulted in a longer time to effect onset (1.4 +/- 0.2 vs. 0.5 +/- 0.1 min, EEG) and a trend for delayed anesthetic recovery (26.8 +/- 9.4 vs. 17 +/- 3.5 min, EEG; 26.1 +/- 8.8 vs. 16.8 +/- 3.3 min, sleep). In study 2, coadministration of drug-free emulsion with propofol did not alter the time course of effect. In study 3, more than twice the dose of propofol was required to achieve EEG burst suppression with the lipid-free formulation. Two animals died after administration of propofol to EEG burst suppression with the lipid-free formulation; no deaths occurred in the emulsion group.

Conclusion

The incorporation of propofol in emulsion reduces dose requirements and produces rapid onset and recovery of anesthetic effect.
Dose-dependent Effects of Halothane on the Phrenic Nerve Responses to Acute Hypoxia in Vagotomized Dogs
Authors: Stuth Eckehard A. E. , Dogas Zoran , Krolo Mirko , Kampine John P. , Hopp Francis A. , Zuperku Edward J.
Published: November 2003

Background

Previous studies in dogs and humans suggest that the carotid body chemoreceptor response to hypoxia is selectively impaired by halothane. The present studies in an open-loop canine preparation were performed to better delineate the effects of anesthetic concentrations of halothane on the carotid body chemoreceptor-mediated phrenic nerve response to an acute hypoxic stimulus.

Methods

Three protocols were performed to study the effects of halothane anesthesia on the phrenic nerve response to 1 min of isocapnic hypoxia (partial pressure of oxygen [PaO2] at peak hypoxia, 35-38 mmHg) in unpremedicated, anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. In protocol 1, the dose-dependent effects of halothane from 0.5-2.0 minimum alveolar concentration (MAC) on the hypoxic response during moderate hypercapnia (partial pressure of carbon dioxide [PaCO2], 60-65 mmHg) were studied in 10 animals. In protocol 2, the hypoxic responses at 1 MAC halothane near normocapnia (PaCO2, 40-45 mmHg) and during moderate hypercapnia were compared in an additional four animals. In protocol 3, the hypoxic response of 4 of 10 dogs from protocol 1 was also studied under sodium thiopental (STP) anesthesia after they completed protocol 1.

Results

Protocol 1: Peak phrenic nerve activity (PPA) increased significantly during the hypoxic runs compared with the isocapnic hyperoxic controls at all halothane doses. The phrenic nerve response to the hypoxic stimulus was present even at the 2 MAC dose. Protocol 2: The net hypoxic responses for the two carbon dioxide background levels at 1 MAC were not significantly different. Protocol 3: The net hypoxic response of PPA for the STP anesthetic was not significantly different from the 1 MAC halothane dose. Bilateral carotid sinus denervation abolished the PPA response to hypoxia.

Conclusions

The phrenic nerve response to an acute, moderately severe isocapnic hypoxic stimulus is dose-dependently depressed but not abolished by surgical doses of halothane. This analysis does not suggest a selective depression of the carotid body chemoreceptor response by halothane. The observed hypoxic phrenic response was mediated by the carotid body chemoreceptors in vagotomized dogs because bilateral carotid sinus denervation abolished all increases in PPA.
Effects of Halothane on the Phrenic Nerve Responses to Carbon Dioxide Mediated by Carotid Body Chemoreceptors in Vagotomized Dogs
Authors: Stuth Eckehard A. E. , Dogas Zoran , Krolo Mirko , Kampine John P. , Hopp Francis A. , Zuperku Edward J.
Published: November 2003

Background

Previous studies in dogs showed that the phrenic nerve response to an acute hypoxic stimulus was dose dependently depressed by 0.5-2.0 minimum alveolar concentration (MAC) of halothane but not abolished. Because a carbon dioxide stimulus is transduced by a different mechanism in the carotid body chemoreceptors (CBCRs) than is a hypoxic stimulus, inhalational anesthetics may preferentially depress one of these transduction processes, the central neuronal processing, or both, of the integrated responses to these two types of inputs.

Methods

Carotid body chemoreceptor stimulation was produced by short (1-1.5 s), bilateral, 100% carbon dioxide in saline infusions into the carotid arteries during neural inspiration in unpremedicated, halothane-anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. The phrenic neurogram quantified the neural inspiratory response. Four protocols were performed in the study: (1) the dose-dependent effects of halothane anesthesia (0.5-2.0 MAC) during hyperoxic hypercapnia on phrenic nerve activity, (2) the effects of three background levels of the partial pressure of carbon dioxide (PaCO2) on the magnitude of the carbon dioxide infusion responses at 1 MAC halothane, (3) the effects of anesthetic type on the magnitude of the carbon dioxide infusion response, and (4) the effects of CBCR denervation.

Results

Peak phrenic nerve activity (PPA) increased significantly during the carbon dioxide-stimulated phrenic burst in protocols 1-3; after denervation there was no response (protocol 4). Halothane produced a dose-dependent reduction in the PPA of control and carbon dioxide infusion-stimulated phrenic bursts and in the net carbon dioxide response. The net PPA responses for the different PaCO2 background levels were not different but were somewhat larger for sodium thiopental anesthesia than for 1.0 MAC halothane.

Conclusions

The phrenic nerve response to an acute, severe carbon dioxide stimulus was dose dependently depressed by surgical doses of halothane. The observed responses to carbon dioxide infusion were mediated by the CBCRs because they were eliminated by CBCR denervation. These results suggest that the CBCR transduction and central transmission of the carbon dioxide signal in terms of inspiratory excitatory drive are not abolished at surgical levels of halothane anesthesia.
Involvement of Cerulospinal Glutamatergic Neurotransmission in Fentanyl-induced Muscular Rigidity in the Rat
Authors: Fu Miin-Jiuan , Tsen Le-Yin , Lee Tak-Yu , Lui Ping-Wing , Chan Samuel H. H.
Published: November 2003

Background

Investigators in the authors' laboratory previously established the critical participation of the cerulospinal noradrenergic pathway in muscular rigidity elicited by fentanyl. The identification of colocalization of glutamate with tyrosine hydroxylase in most locus ceruleus neurons suggests a role for cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity. This suggestion and the subtype(s) of glutamate receptors involved were investigated here.

Methods

Electromyographic signals activated by bilateral microinjection of 2.5 microg fentanyl into the locus ceruleus were recorded differentially from the left sacrococcygeus dorsi lateralis muscle of adult male Sprague-Dawley rats. The effect of intrathecal administration at the lower lumbar spinal cord of various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or agonists on this index of muscular rigidity was studied. Rats were under mechanical ventilation, and intravenous infusion of ketamine (30 mg x kg(-1) x h(-1)) was maintained until 10 min before fentanyl was administered.

Results

Microinjection of fentanyl bilaterally into the locus ceruleus increased the root mean square and decreased the mean power frequency values of electromyographic signals. The efficacy of fentanyl to elicit muscular rigidity in this manner was significantly reduced by previous intrathecal administration of either 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), D-(-)-2-amino-5-phosphonovaleric acid (AP5), or (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). Intrathecal administration of kainic acid or NMDA also resulted in significant electromyographic activation.

Conclusions

In addition to the cerulospinal noradrenergic mechanism, the cerulospinal glutamatergic pathway and both NMDA and non-NMDA receptors in the spinal cord may mediate fentanyl-induced muscular rigidity in the rat.
Interaction between Anesthetics and the Sodium-Hydrogen Exchange Inhibitor HOE 642 (Cariporide) in Ischemic and Reperfused Rat Hearts
Authors: Mathur Sanjiv , Karmazyn Morris
Published: November 2003

Background

Sodium (Na+)-hydrogen (H+) exchange (NHE) inhibitors are effective cardioprotective agents. The potent NHE inhibitor HOE 642 (cariporide) is being evaluated clinically in high-risk patients, including those having coronary artery bypass. Volatile anesthetics are also cardioprotective, most likely via different mechanisms. The potential interaction between anesthetics and HOE 642 was investigated.

Methods

Electrically paced isolated rat hearts were perfused at constant flow. Left ventricular developed pressure and end-diastolic pressure were monitored as determinants of function. Hearts were subjected to 60 min each of total ischemia followed by reperfusion. Isoflurane (0.93 minimum alveolar concentration [MAC]), sevoflurane (1.03 MAC), or sufentanil (1.2 nM) was added 15 min before ischemia and throughout reperfusion, either alone or in combination with HOE 642 (5 microM). The effect of HOE 642 alone was also studied. At the end of reperfusion, hearts were freeze-clamped for subsequent determination of tissue metabolites.

Results

In control hearts, left ventricular developed pressure recovered to 40% of preischemia values, whereas left ventricular end-diastolic pressure increased by 650% after reperfusion. Sevoflurane, isoflurane, or HOE 642 alone significantly enhanced left ventricular developed pressure recovery to more than 90%, although recovery with HOE 642 was more rapid and accompanied by significantly reduced left ventricular end-diastolic pressure. HOE 642 plus volatile anesthetics produced additive effects, with left ventricular developed pressure recovering by more that 100%, although left ventricular end-diastolic pressure was not further reduced. Sufentanil had no effect in terms of developed pressure, but protection with HOE 642 was maintained. HOE 642 with or without volatile anesthetics also preserved adenosine triphosphate levels.

Conclusions

Isoflurane, sevoflurane, and HOE 642 enhance ventricular recovery, but the effect of HOE 642 is also associated with reduced contracture and adenosine triphosphate preservation. A combination of the NHE inhibitor and either volatile agent confers additive and superior protection, which could be relevant for the establishment of ideal cardioprotective strategies during surgery.
Inhibition of Nitric Oxide Synthase Decreases Anesthetic Requirements of Intravenous Anesthetics in Xenopus laevis
Authors: Tonner Peter H. , Scholz Jeans , Lamberz Lars , Schlamp Nikolas , Schulte am Esch Jochen
Published: November 2003

Background

Acute inhibition of nitric oxide synthase (NOS) has been demonstrated to reduce the anesthetic requirements of volatile anesthetics. Recent data suggest that not only volatile but also intravenous anesthetic agents interact with nitric oxide (NO) metabolism. The aim of this study was to examine the effect of NOS inhibition by nitroG-L-arginine-methyl-ester (L-NAME) on the anesthetic action of the intravenous anesthetics thiopental, propofol, and ketamine.

Methods

The anesthetic potencies of thiopental, propofol, and ketamine were determined in Xenopus laevis tadpoles in the absence and presence of L-NAME. Anesthesia was defined as loss of righting reflex for 5 s. A nonlinear logistic regression curve was fitted to the data and half-maximal effective concentrations (EC50) were calculated. A second set of experiments was performed with different concentrations of L-NAME in the presence of the previously determined the EC50 of the intravenous anesthetics.

Results

The EC50s of the anesthetics thiopental, propofol, and ketamine were determined to be 25.5 +/- 2.0 microM, 1.9 +/- 0.1 microM, and 59.7 +/- 0.7 microM, respectively. The addition of L-NAME shifted the concentration-response curves to the left in a concentration-dependent manner. In the presence of 1 mM L-NAME, the EC50 of thiopental was reduced by 43%, the EC50 of propofol by 26%, and the EC50 of ketamine by 63%. The addition of D-NAME did not change the EC50 values of the three anesthetics. In the presence of L-arginine, the effect of L-NAME on the EC50 of thiopental was reversed. When administered by itself in a concentration range from 0.1 microM to 10 mM, L-NAME did not alter the behavior of the tadpoles.

Conclusions

The results of the present study show that acute inhibition of NOS by L-NAME results in reduced anesthetic requirements of the intravenous anesthetics thiopental, propofol, and ketamine. This interaction of acutely administered L-NAME and intravenous anesthetics indicates that the NO-cyclic guanosine 3',5'-monophosphate system is involved in mediating the anesthetic effect of these compounds.
Experimental Subarachnoid Hemorrhage in Rats
Authors: Cole Daniel J. , Nary Jeffrey C. , Reynolds Lowell W. , Patel Piyush M. , Drummond John C.
Published: November 2003

Background

Hemodilution with diaspirin crosslinked hemoglobin (DCLHb) ameliorates occlusive cerebral ischemia. However, subarachnoid hemoglobin has been implicated as a cause of cerebral hypoperfusion. The effect of intravenous DCLHb on cerebral perfusion and neuronal death after experimental subarachnoid hemorrhage was evaluated.

Methods

Rats (n = 48) were anesthetized with isoflurane and subarachnoid hemorrhage was induced by injecting 0.3 ml of autologous blood into the cistema magna. Each animal received one of the following regimens: Control, no hematocrit manipulation; DCLHb, hematocrit concentration decreased to 30% with DCLHb; or Alb, hematocrit concentration decreased to 30% with human serum albumin. The experiments had two parts, A and B. In part A, after 20 min, cerebral blood flow (CBF) was assessed with 14C-iodoantipyrine autoradiography. In part B, after 96 h, in separate animals, the number of dead neurons was determined in predetermined coronal sections by hematoxylin and eosin staining.

Results

Cerebral blood flow was greater for the DCLHb group than for the control group; and CBF was greater for the Alb group than the other two groups (P < 0.05). In one section, CBF was 45.5 +/- 10.9 ml x 100 g(-1) x min(-1) (mean +/- SD) for the control group, 95.3 +/- 16.6 ml x 100 g(-1) x min(-1) for the DCLHb group, and 138.1 +/- 18.7 ml x 100 g(-1) x min(-1) for the Alb group. The number of dead neurons was less in the Alb group (611 +/- 84) than in the control group (1,097 +/- 211), and was less in the DCLHb group (305 +/- 38) than in the other two groups (P < 0.05).

Conclusions

These data support a hypothesis that hemodilution decreases hypoperfusion and neuronal death after subarachnoid hemorrhage. The data do not support the notion that intravascular molecular hemoglobin has an adverse effect on brain injury after subarachnoid hemorrhage.
Prophylactic Atenolol Reduces Postoperative Myocardial Ischemia
Authors: Wallace Arthur , Layug Beth , Tateo Ida , Li Juliet , Hollenberg Milton , Browner Warren , Miller David , Mangano Dennis T.
Published: November 2003

Background

Perioperative myocardial ischemia occurs in 20-40% of patients at risk for cardiac complications and is associated with a ninefold increase in risk for perioperative cardiac death, myocardial infarction, or unstable angina, and a twofold long-term risk. Perioperative atenolol administration reduces the risk of death for as long as 2 yr after surgery. This randomized, placebo-controlled, double-blinded trial tested the hypothesis that perioperative atenolol administration reduces the incidence and severity of perioperative myocardial ischemia, potentially explaining the observed reduction in the risk for death.

Methods

Two-hundred patients with, or at risk for, coronary artery disease were randomized to two study groups (atenolol and placebo). Monitoring included a preoperative history and physical examination and daily assessment of any adverse events. Twelve-lead electrocardiography (ECG), three-lead Holter ECG, and creatinine phosphokinase with myocardial banding (CPK with MB) data were collected 24 h before until 7 days after surgery. Atenolol (0, 5, or 10 mg) or placebo was administered intravenously before induction of anesthesia and every 12 h after operation until the patient could take oral medications. Atenolol (0, 50, or 100 mg) was administered orally once a day as specified by blood pressure and heart rate.

Results

During the postoperative period, the incidence of myocardial ischemia was significantly reduced in the atenolol group: days 0-2 (atenolol 17 of 99 patients; placebo, 34 of 101 patients; P = 0.008) and days 0-7 (atenolol, 24 of 99 patients; placebo, 39 of 101 patients; P = 0.029). Patients with episodes of myocardial ischemia were more likely to die in the next 2 yr (P = 0.025).

Conclusions

Perioperative administration of atenolol for 1 week to patients at high risk for coronary artery disease significantly reduces the incidence of postoperative myocardial ischemia. Reductions in perioperative myocardial ischemia are associated with reductions in the risk for death at 2 yr.
The Effects of Fentanyl on Sevoflurane Requirements for Loss of Consciousness and Skin Incision
Authors: Katoh Takasumi , Ikeda Kazuyuki
Published: November 2003

Background

Fentanyl produces a minimal reduction in the minimum alveolar concentration of sevoflurane to prevent response to a verbal command in 50% of patients (MAC[awake]) at low but analgesic plasma concentrations. The reduction in MAC(awake), however, is still unknown at higher fentanyl concentrations. The reduction in the MAC of sevoflurane by fentanyl has not been described accurately. The purpose of this study was to determine the MAC(awake) and MAC reduction of sevoflurane by fentanyl.

Methods

Ninety-two patients were randomly allocated to seven fentanyl concentration groups (target plasma concentrations of 0, 1, 1.5, 3, 6, 10, and 14 ng/ml). Responses to verbal command were observed for MAC(awake) assessment at predetermined sevoflurane concentrations. Thereafter, in patients whose target fentanyl concentration was 0 to 10 ng/ml, responses to skin incision were observed for MAC assessment at new steady-state sevoflurane concentrations. The reduction in the MAC(awake) and MAC of sevoflurane by the measured fentanyl concentration was calculated.

Results

There was an initial steep reduction in the MAC of sevoflurane by fentanyl, with 3 ng/ml resulting in a 59% MAC reduction. A ceiling effect was observed, with 10 ng/ml providing only a further 17% reduction in MAC. The initial reduction in MAC(awake) was not as steep as that in MAC. Fentanyl reduced MAC(awake) by approximately 24% at a plasma concentration of 3 ng/ml. Although the reduction curve of MAC(awake) was parabolic, no manifest ceiling effect was observed at concentrations administered in the present study.

Conclusions

The reduction in sevoflurane requirements for loss of consciousness and skin incision by fentanyl was determined. Fentanyl reduced both requirements, but the mode of the reduction was not comparable.
Bispectral Analysis of the Electroencephalogram Predicts Conscious Processing of Information during Propofol Sedation and Hypnosis
Authors: Kearse Lee A. , Rosow Carl , Zaslavsky Alan , Connors Patricia , Dershwitz Mark , Denman William
Published: November 2003

Background

The bispectral index (BIS) measures changes in the interfrequency coupling of the electroencephalogram (EEG). The purposes of this study were (1) to determine whether BIS correlates with responses to command during sedation and hypnosis induced by propofol or propofol and nitrous oxide, and (2) to compare BIS to targeted and measured concentrations of propofol in predicting participants' responses to commands.

Methods

Twenty volunteers (15 men and 5 women, aged 22-50 yr) were given propofol by computer-controlled infusion, and EEG was recorded for off-line analysis of BIS. Responses to randomly ordered verbal commands or voice plus touch were measured with two categorical scales (CS1 and CS2, respectively). All subjects received a propofol infusion targeted to achieve effect site concentrations of 1, 2, 4, 2, 1, and 0 microg/ml. Ten participants had repeated infusion, whereas 10 others breathed 30% nitrous oxide and oxygen and received a propofol infusion targeted for 0.5, 1, 2, 4, 2, 1, 0.5, and 0 microg/ml. Five minutes after each targeted concentration had been reached, CS1, CS2, and arterial propofol concentration were determined. The area under the receiver operating characteristic curve was used to compare the accuracy of (1) BIS, (2) targeted propofol concentration, (3) measured concentration, and (4) treatment history as predictors of response.

Results

Bispectral index was a strong predictor of CS1 and CS2 (P < 0.0001) and significantly more accurate than targeted or measured propofol concentrations (P < 0.0003 and P < 0.003, respectively). It also provided additional predictive power when combined with treatment history (P < 0.02). Nitrous oxide slightly decreased the probability of response at a given value of BIS (P < 0.05), but accuracy was unaffected.

Conclusions

Bispectral index accurately predicts response to verbal commands during sedation and hypnosis with propofol or propofol plus nitrous oxide. Accuracy is maintained in situations likely to be encountered during clinical use: when propofol concentrations are increasing or decreasing and when repeated measurements are made over time.
Fentanyl Augments the Blockade of the Sympathetic Response to Incision (MAC-BAR) Produced by Desflurane and Isoflurane
Authors: Daniel Malcolm , Weiskopf Richard B. , Noorani Mariam , Eger Edmond I.
Published: November 2003

Background

Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner.

Methods

Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 microg/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group.

Results

Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 microg/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P < 0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 microg/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC).

Conclusions

Clinically attainable doses of desflurane and isoflurane, in 60% nitrous oxide (0.55 MAC), block the cardiovascular response to surgical incision at 1.3 MAC. Fentanyl given at 1.5 microg/kg decreases the MAC-BAR for each agent with no further decrease produced by 3 microg/kg fentanyl.
Accuracy of a Cerebral Oximeter in Healthy Volunteers under Conditions of Isocapnic Hypoxia
Authors: Henson Lindsey C. , Calalang Carolyn , Temp John A. , Ward Denham S.
Published: November 2003

Background

A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near infrared spectroscopy. The accuracy of a commercially available oximeter was tested in healthy volunteers by precisely controlling end-tidal oxygen (P[ET]O2) and carbon dioxide (P[ET]CO2) tensions to alter global cerebral oxygen saturation.

Methods

In 30 healthy volunteers, dynamic end-tidal forcing was used to produce step changes in P[ET]O2 resulting in arterial saturation ranging from approximately 70% to 100% under conditions of controlled normocapnia (each person's resting P[ET]CO2) or hypercapnia (resting plus 7-10 mmHg). Blood arterial (SaO2) and jugular bulb venous (S[jv]O2) saturations during each P(ET)O2 interval were determined by co-oximetry. The cerebral oximeter reading (rSO2) and an estimated jugular venous saturation (S[jv]O2), derived from a combination of SaO2 and rSO2, were compared with the measured S(jv)O2.

Results

The S(jv)O2 was significantly higher with hypercapnia than with normocapnia for the same SaO2. The rSO2 and S(jv)O2 were both highly correlated with S(jv)O2 for individual volunteers (mean r2 = 0.91 for each relation); however, the slopes and intercepts varied widely among volunteers. In three of them, the cerebral oximeter substantially underestimated the measured S(jv)O2.

Conclusions

During isocapnic hypoxia in healthy persons, cerebral oxygenation as estimated by near infrared spectroscopy precisely tracks changes in measured S(jv)O2 within individuals, but the relation exhibits a wide range of slopes and intercepts. Therefore the clinical utility of the device is limited to situations in which tracking trends in cerebral oxygenation would be acceptable.
Low-dose Ondansetron with Dexamethasone More Effectively Decreases Vomiting after Strabismus Surgery in Children than Does High-dose Ondansetron
Authors: Splinter William M. , Rhine Elliot J.
Published: November 2003

Background

Ondansetron and dexamethasone have been observed to decrease the incidence of vomiting by children after general anesthesia. This study compared the effect of high-dose (150 microg/kg) ondansetron with low-dose (50 microg/kg) ondansetron plus 150 microg/kg dexamethasone on the incidence of vomiting after strabismus in children.

Methods

This study had a double-blind, blocked, stratified, randomized design. With parental consent and Hospital Ethics Committee approval, healthy children aged 2-14 yr who were undergoing elective strabismus surgery were studied. Anesthesia was induced intravenously with propofol or by inhalation with halothane and nitrous oxide. Patients in the high-dose group were given placebo plus 150 microg/kg (maximum dose, 8 mg) of ondansetron intravenously, whereas patients in the low-dose group were given 150 microg/kg dexamethasone (maximum dose, 8 mg) and 50 microg/kg ondansetron intravenously in a double-blind manner. Anesthesia was maintained with halothane and nitrous oxide. All incidences of vomiting occurring as long as 24 h after anesthesia were recorded.

Results

Three of the 200 patients enrolled in the study were excluded from data analysis. The groups were similar with respect to demographic data and potential confounding variables. Patients vomited from 0-12 times. The low-dose ondansetron plus dexamethasone group had a lower incidence of vomiting, 9% (95% CI = 4-17%) versus 28% (95% CI = 20-38%; P < 0.001). Only 1% of the patients in the low-dose ondansetron plus dexamethasone group vomited while in the hospital.

Conclusions

Low-dose ondansetron plus dexamethasone is an effective prophylactic antiemetic combination for children undergoing strabismus surgery.
Headache after Attempted Epidural Block
Authors: Aida Sumihisa , Taga Kiichiro , Yamakura Tomohiro , Endoh Hiroshi , Shimoji Koki
Published: November 2003

Background

Postmeningeal puncture headache (PMPH) is typically attributed to the loss of cerebrospinal fluid (CSF). However, when it occurs after an attempted epidural puncture, it may be due to either CSF loss or, potentially, to the subarachnoid injection of air used as a part of "loss-of-resistance" testing. This study was performed to examine the relation between intrathecal air and PMPH.

Methods

Using a loss-of-resistance test with an air-filled (n = 1,812; air group) or saline-filled (n = 1,918; saline group) syringe, epidural block was performed in patients with acute or chronic pain. The dura was judged to be perforated not only when backflow of CSF was recognized in the needle but also when signs and symptoms solely attributable to meningeal perforation were seen, such as high spinal blockade or severe motor blockade. The incidence, onset time, and duration of PMPH in the air and saline groups were compared. In all patients with signs of meningeal perforation, brain computed tomography was examined.

Results

The incidence of PMPH in the air group (32 cases) was significantly higher than that in the saline group (5 cases), although the occurrences of meningeal perforation between the air (48 cases) and saline (51 cases) groups did not differ significantly. Intrathecal air bubbles were detected on brain computed tomography in both the deep supraspinal structures such as the ventricles, Silvian fissures and cisterns, and the superficial subarachnoid space in 30 of 32 patients with PMPH in the air group, whereas no intrathecal air bubbles were seen in the saline group. PMPH was significantly more rapid in onset and shorter in duration in the air group than that in the saline group.

Conclusions

The use of air for loss-of-resistance testing during epidural block was associated with a higher incidence of PMPH, which might be attributable to subarachnoid air injection and CSF leakage.