bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Ketamine and Its Enantiomers on the Morphine- or Dexmedetomidine-induced Antinociception after Intrathecal Administration in Rats
Authors: Joó Gabriella , Horvath Gyöngyi , Klimscha Walter , Kekesi Gabriella , Dobos Ildiko , Szikszay Margit , Benedek György
Published: November 2003

Background

The spinal administration of some N-methyl-d-aspartate receptor antagonists results in antinociception and potentiates the effects of opioids and alpha2-adrenoceptor agonists, but ketamine and its enantiomers have not been examined. The present study investigated the interactions of racemic ketamine, R(-)-ketamine and S(+)-ketamine with morphine and with dexmedetomidine.

Methods

Intrathecal catheters were implanted into male Wistar rats. Three days later, the acute nociceptive sensitivity was assessed using the tail-flick test. Analgesic latencies were converted to the percentage maximum possible effect. The dose that yielded 50% of the maximum possible effect (ED50) and dose-response and time-course curves were determined for the ketamines (30-300 microg), morphine (0.1-3.0 microg), dexmedetomidine (0.3-10.0 microg), and mixtures of two doses of ketamines (30 or 100 microg) with different doses of morphine or dexmedetomidine for fixed-dose analysis.

Results

Neither racemic ketamine nor its enantiomers alone had a significant effect on the tail-flick test, with the exception of the highest dose of racemic ketamine, which caused motor impairment. Morphine and dexmedetomidine each produced dose-dependent antinociception, with ED50 of 1.7 microg (95% confidence interval: 1.04-2.32) and 4. 85 microg (3.96-5.79), respectively. A low dose (30 microg) of racemic ketamine or its enantiomers did not influence the ED50 of morphine significantly. Coadministration of 100 microg racemic ketamine or S(+)-ketamine, but not R(-)-ketamine, significantly enhanced and prolonged the antinociceptive effect of morphine. Both doses of racemic ketamine or its isomers significantly decreased the ED50 value for dexmedetomidine, although the higher dose of racemic or S(+)-ketamine had the highest potency. One-hundred micrograms of racemic ketamine or S(+)-ketamine also prolonged the effects of dexmedetomidine.

Conclusions

These data indicate that racemic ketamine and S(+)-ketamine, but not R(-)-ketamine, exhibit similar effectiveness in potentiating the antinociceptive effects of both morphine and dexmedetomidine.
Intraoperative Cerebral Arterial Embolization during Total Hip Arthroplasty
Authors: Edmonds Chris R. , Barbut Denise , Hager David , Sharrock Nigel E.
Published: November 2003

Background

Fat embolism to the pulmonary circulation is known to occur during total hip arthroplasty, especially during insertion of a cemented femoral component. Fat and air bubbles may enter the systemic circulation via a patent foramen ovale or through pulmonary circulation.

Methods

To determine whether microemboli to the brain were occurring during total hip arthroplasty, 23 patients underwent transcranial Doppler assessment of emboli to the middle cerebral artery during total hip arthroplasty. Surgery was performed with the patient in the lateral decubitus position so that the probe recorded from the nondependent side.

Results

Successful recordings were made in 20 patients, in 8 of 20 patients there were embolic signals, which ranging from 1 to 200. In all eight patients, signals were recorded during impaction of a cemented component or after relocation of the hip. Only one patient showed evidence of emboli with impaction of the acetabulum component. In two patients there were 150 and 200 embolic signals: in both mild respiratory symptoms developed. One patient became overtly agitated during a flurry of emboli.

Conclusion

Cerebral microemboli can occur during total hip arthroplasty. Whether this contributes to changes in postoperative cognitive function is unknown.
Omission of Nitrous Oxide from a Propofol-based Anesthetic Does Not Affect the Recovery of Women Undergoing Outpatient Gynecologic Surgery
Authors: Arellano Ramiro J. , Pole Meena L. , Rafuse Sara E. , Fletcher Mary , Saad Yousri G. , Friedlander Mark , Norris Andrew , Chung Frances F. T.
Published: November 2003

Background

Although nitrous oxide (N2O) is used commonly during anesthesia, clinically relevant advantages-disadvantages of using this agent are not well established in the ambulatory setting. This study in women undergoing ambulatory gynecologic surgery compares outcomes in patients administered total intravenous anesthesia with propofol versus the propofol plus N2O. The primary outcome was the time to home readiness. Secondary outcomes included the incidence of postanesthetic adverse events.

Methods

Women presenting for elective ambulatory termination of pregnancy or gynecologic laparoscopy were induced with an intravenous sleep dose of propofol and fentanyl. After induction, subjects were randomly allocated to maintenance anesthesia with propofol alone or propofol plus 65% N2O. Patients were assessed by a blinded observer in the postanesthetic care unit at 20-min intervals to determine home readiness. Postoperative pain and nausea were measured with visual analog scales. Postoperative analgesics and antiemetics were recorded. The incidence of adverse events occurring after hospital discharge was assessed by a telephone interview 24 h postoperatively.

Results

A total of 740 patients received propofol alone, and 750 patients received propofol plus N2O. Mean home readiness times were not significantly different between treatment groups. There were no significant differences between groups in pain scores, nausea scores, analgesia administration, or antiemetic administration before discharge. There were no significant differences in the frequency of adverse events for 24 h after discharge from hospital.

Conclusions

Omission of N2O from a propofol-based anesthetic for ambulatory gynecologic surgery does not affect time to home readiness or the incidence of postoperative adverse events up to 24 h after discharge from hospital. (Key words: Awareness; outpatient surgery; total intravenous anesthesia.)
Preanesthetic Train-of-four Fade Predicts the Atracurium Requirement of Myasthenia Gravis Patients
Authors: Mann Ruth , Blobner Manfred , Jelen-Esselborn Sabine , Busley Raimund , Werner Christian
Published: November 2003

Background

The most sensitive diagnostic criterion of myasthenia gravis is a decrement in the muscular response to repetitive stimulation. The authors hypothesized that myasthenia gravis patients who show a train-of-four ratio (T4/T1) < 0.9 in the preanesthetic period will have increased sensitivity to nondepolarizing neuromuscular blocking agents compared with myasthenia gravis patients with preanesthetic T4/T1 > or = 0.9.

Methods

After institutional review board approval was obtained, 20 electrophysiologically documented myasthenia gravis patients were studied. Current pyridostigmine therapy was continued until the morning of surgery. Before induction of anesthesia, neuromuscular transmission was recorded from the hypothenar muscles using electromyography with train-of-four stimulation of the ulnar nerve. According to the T4/T1 ratio, patients were assigned to the "normal" group (T4/T1 > or = 0.9) or the "decrement" group (T4/T1 < 0.9). After induction of intravenous anesthesia, the effective dose to achieve a 95% neuromuscular blockade (ED95) for atracurium was assessed with a cumulative bolus technique. Postoperatively, pyridostigmine was titrated to obtain a T4/T1 > 0.75 and to treat residual myasthenic symptoms.

Results

In 14 patients, preanesthetic T4/T1 was > or = 0.9 (normal), whereas 6 patients presented with T4/T1 < 0.9 (decrement). Decrement patients had a lower ED95 of 0.07 +/- 0.03 mg/kg atracurium (mean +/- SD) compared with normal patients with an ED95 of 0.24 +/- 0.11 mg/kg atracurium (P = 0.002). All patients were extubated within 30 min after surgery. Postoperative pyridostigmine infusion did not differ significantly between groups.

Conclusions

The requirement for atracurium is significantly reduced in myasthenia gravis patients with a T4/T1 ratio < 0.9 before anesthesia. This study indicates that routine neuromuscular monitoring in myasthenia gravis patients should be extended into the preinduction period to identify patients who require less atracurium.
Endotoxin Desensitization of Human Mononuclear Cells after Cardiopulmonary Bypass
Authors: Grundmann Ulrich , Rensing Hauke , Adams Hans-Anton , Falk Sabine , Wendler Olaf , Ebinger Nicole , Bauer Michael
Published: November 2003

Background

The ability of leukocytes to release proinflammatory cytokines on lipopolysaccharide stimulation in vitro is impaired after cardiopulmonary bypass (CPB). This study tested contribution and interaction of humoral factors in altered leukocyte responsiveness to lipopolysaccharide.

Methods

Whole blood and isolated peripheral-blood mononuclear cells (PBMCs) from 10 patients obtained after induction of anesthesia (T1) and 20 min (T2) and 24 h (T3) after CPB were cultured in the absence or presence of lipopolysaccharide and assessed for release of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta and their functional antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10. In addition, dose-response characteristics and interaction of IL-10 and norepinephrine as modulators of TNF-alpha release were studied.

Results

Cardiopulmonary bypass induced release of antiinflammatory (T2: IL-10: median 25 pg/ml, 25th-75th percentile 9-42; IL-1ra: median 1,528 pg/ml, 25th-75th percentile 1,075-17,047; P < 0.05 compared with T1) but failed to induce proinflammatory cytokines (T2: TNF-alpha: median 0 pg/ml, 25th-75th percentile 0-6; IL-1beta: median 1 pg/ml, 25th-75th percentile 0-81; nonsignificant). Removal of plasma at T2 increased TNF-alpha response to lipopolysaccharide (+83.8%; P < 0.05), whereas it suppressed IL-10 (-36.8%; P < 0.05). Similarly, incubation of PBMCs (T1) with plasma obtained after CPB (T2) as well as addition of IL-10 or norepinephrine in concentrations present in plasma after CPB led to a reduced lipopolysaccharide-stimulated TNF-alpha and an increased IL-10 response. Coadministration of norepinephrine and IL-10 had synergistic effects. Although pretreatment with an anti-IL-10 antibody and labetalol before addition of plasma obtained at T2 largely restored the TNF-alpha response in vitro, their addition post-treatment failed to restore the monocytic TNF-alpha response.

Conclusions

Plasma contains interacting factors that inhibit the release of TNF-alpha and increase the release of IL-10, presumably attenuating the inflammatory response to CPB. Although norepinephrine fails to induce a cytokine response in the absence of other stimuli, its administration seems to augment the antiinflammatory IL-10 response while attenuating the TNF-alpha response.
Arterial to End-tidal Carbon Dioxide Pressure Difference during Laparoscopic Surgery in Pregnancy
Authors: Bhavani-Shankar Kodali , Steinbrook Richard A. , Brooks David C. , Datta Sanjay
Published: November 2003

Background

There is controversy about whether capnography is adequate to monitor pulmonary ventilation to reduce the risk of significant respiratory acidosis in pregnant patients undergoing laparoscopic surgery. In this prospective study, changes in arterial to end-tidal carbon dioxide pressure difference (PaCO2--PetCO2), induced by carbon dioxide pneumoperitoneum, were determined in pregnant patients undergoing laparoscopic cholecystectomy.

Methods

Eight pregnant women underwent general anesthesia at 17-30 weeks of gestation. Carbon dioxide pnueumoperitoneum was initiated after obtaining arterial blood for gas analysis. Pulmonary ventilation was adjusted to maintain PetCO2 around 32 mmHg during the procedure. Arterial blood gas analysis was performed during insufflation, after the termination of insufflation, after extubation, and in the postoperative period.

Results

The mean +/- SD for PaCO2--PetCO2 was 2.4 +/- 1.5 before carbon dioxide pneumoperitoneum, 2.6 +/- 1.2 during, and 1.9 +/- 1.4 mmHg after termination of pneumoperitoneum. PaCO2 and pH during pneumoperitoneum were 35 +/- 1.7 mmHg and 7.41 +/- 0.02, respectively. There were no significant differences in either mean PaCO2--PetCO2 or PaCO2 and pH during various phases of laparoscopy.

Conclusions

Capnography is adequate to guide ventilation during laparoscopic surgery in pregnant patients. Respiratory acidosis did not occur when PetCO2 was maintained at 32 mmHg during carbon dioxide pneumoperitoneum.
Acute Opioid Tolerance
Authors: Guignard Bruno , Bossard Anne Elisabeth , Coste Carole , Sessler Daniel I. , Lebrault Claude , Alfonsi Pascal , Fletcher Dominique , Chauvin Marcel
Published: November 2003

Background

Rapid development of acute opioid tolerance is well established in animals and is more likely to occur with large doses of short-acting drugs. The authors therefore tested the hypothesis that intraoperative remifentanil administration results in acute opioid tolerance that is manifested by increased postoperative pain and opioid requirement.

Methods

Fifty adult patients undergoing major abdominal surgery were randomly assigned to two anesthetic regimens: (1) desflurane was kept constant at 0.5 minimum alveolar concentrations and a remifentanil infusion was titrated to autonomic responses (remifentanil group); or (2) remifentanil at 0.1 microg. kg-1. min-1 and desflurane titrated to autonomic responses (desflurane group). All patients were given a bolus of 0.15 mg/kg morphine 40 min before the end of surgery. Morphine was initially titrated to need by postanesthesia care nurses blinded to group assignment. Subsequently, patients-who were also blinded to group assignment-controlled their own morphine administration. Pain scores and morphine consumption were recorded for 24 postoperative h.

Results

The mean remifentanil infusion rate was 0.3 +/- 0.2 microg. kg-1. min-1 in the remifentanil group, which was significantly greater than in the desflurane group. Intraoperative hemodynamic responses were similar in each group. Postoperative pain scores were significantly greater in the remifentanil group. These patients required morphine significantly earlier than those in the desflurane group and needed nearly twice as much morphine in the first 24 postoperative h: 59 mg (25-75% interquartile range, 43-71) versus 32 mg (25-75% interquartile range, 19-59; P < 0.01).

Conclusions

Relatively large-dose intraoperative remifentanil increased postoperative pain and morphine consumption. These data suggest that remifentanil causes acute opioid tolerance and hyperalgesia.
Subarachnoid Meperidine (Pethidine) Causes Significant Nausea and Vomiting during Labor
Authors: Booth John V. , Lindsay David R. , Olufolabi Adeyemi J. , El-Moalem Habib E. , Penning Donald H. , Reynolds James D.
Published: November 2003

Background

The combined spinal-epidural (CSE) technique using bupivicaine-fentanyl has become an established method of pain control during parturition. One limitation is the relatively short duration of effective analgesia produced by bupivicaine-fentanyl. In contrast, subarachnoid meperidine has been shown to provide a long duration of anesthesia in nonobstetric patients. Therefore, the authors tested the hypothesis that subarachnoid meperidine produces a significant increase in the duration of analgesia compared with bupivicaine-fentanyl.

Methods

Based on a power analysis of preliminary data, the authors intended to recruit 90 patients for the study, randomized to three groups: 2.5 mg bupivicaine-25 microg fentanyl, 15 mg meperidine, or 25 mg meperidine. However, after enrolling 34 patients, the study was discontinued because of a significant increase in nausea or vomiting in the study patients.

Results

Nausea or vomiting was substantially increased in both meperidine groups compared with the bupivicaine-fentanyl group: 16 with nausea or vomiting in the meperidine groups (n = 21), compared with 1 in the bupivicaine-fentanyl group (n = 11), P = 0.0011. The mean duration of analgesia provided by 25 mg meperidine was 126 +/- 51 min, compared with 98 +/- 29 min for bupivicaine-fentanyl and 90 +/- 67 min for 15 mg meperidine. These data were not significant (P = 0.27).

Conclusions

Although intrathecal meperidine could potentially prolong subarachnoid analgesia during labor, its use was associated with a significant incidence of nausea or vomiting. These data do not support the use of subarachnoid meperidine in doses of 15 or 25 mg for labor analgesia.
Propofol Selectively Attenuates Endothelium-dependent Pulmonary Vasodilation in Chronically Instrumented Dogs
Authors: Kondo Uruo , Kim Si-Oh , Murray Paul A.
Published: November 2003

Background

The objective was to investigate the effects of propofol anesthesia on the pulmonary vascular response to endothelium-dependent and -independent vasodilators, compared with the responses measured in the conscious state.

Methods

Twenty-six conditioned, male, mongrel dogs were instrumented long-term to measure the left pulmonary vascular pressure-flow relation. Pressure-flow plots were measured on separate days in conscious and propofol-anesthetized (5.0 mg/kg plus 0.5 mg. kg-1. min-1 intravenously) dogs at baseline, after preconstriction with the thromboxane mimetic U46619, and during the cumulative intravenous administration of endothelium-dependent (acetylcholine and bradykinin) and -independent (proline-nitric oxide) vasodilators.

Results

Propofol had no effect on the baseline pressure-flow relation compared with the conscious state. A lower (P < 0.05) dose of U46619 was necessary to achieve the same degree of preconstriction during propofol anesthesia. The pulmonary vasodilator responses to bradykinin and proline-nitric oxide were similar in the conscious and propofol-anesthetized states. In contrast, the pulmonary vasodilator response to acetylcholine was markedly attenuated (P < 0.01) during propofol anesthesia. The intralipid vehicle for propofol had no effect on the acetylcholine dose-response relation.

Conclusion

These results suggest that propofol causes a specific defect in the signal transduction pathway for acetylcholine-induced pulmonary vasodilation. This defect involves the endothelial and not the vascular smooth muscle component of the response.
Effects of Propofol on Hippocampal Synaptic Transmission in Behaving Rats
Authors: Tanner Kylie M. , Obasi Chinyere , Herrick Ian A. , Leung L. Stan
Published: November 2003

Background

The action of propofol has been studied in vitro and in vivo, but the effects of intravenously administered propofol on synaptic transmission in freely behaving rats have not been studied before.

Methods

Rats were implanted with recording electrodes in the dentate gyrus and with stimulation electrodes in the medial perforant path (MPP). Paired pulses at different interpulse intervals (IPIs) were delivered to the MPP, and average evoked potentials were recorded in the dentate gyrus before and after a bolus of propofol (10 or 20 mg/kg administered intravenously) or control vehicle was injected via femoral vein cannula. Because of the layered structure of the hippocampus, population excitatory postsynaptic potentials and population spikes could be distinguished and analyzed.

Results

Propofol has no significant effect on the population excitatory postsynaptic potentials or population spike evoked by a single MPP stimulus pulse. However, paired-pulse inhibition of the dentate population spikes was increased at IPI of 20 and 30 ms. Paired-pulse inhibition of the population spike was most prominent when tail pinch response was lost (deep and moderate anesthesia), but it persisted during light anesthesia. At 200 ms IPI, paired-pulse facilitation of population spikes was observed during moderate anesthesia in most rats.

Conclusions

In freely behaving rats, intravenous propofol enhanced paired-pulse inhibition at < 50 ms IPI, likely by enhancing gamma-aminobutyric acid A receptor-mediated inhibition. Propofol also increased paired-pulse facilitation at 200 ms IPI through an unknown mechanism, which may contribute to the neuroexcitatory effect of propofol.
Effect of Pretreatment with Intrathecal Excitatory Amino Acid Receptor Antagonists on the Development of Pain Behavior Caused by Plantar Incision
Authors: Pogatzki Esther M. , Zahn Peter K. , Brennan Timothy J.
Published: November 2003

Background

Drugs that block spinal excitatory amino acid receptor activation may prevent pain after surgery. The authors previously studied the effect of excitatory amino acid receptor antagonists after incision. In the present study, we examined the role of N-methyl-d-aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors (mGluRs) on the development of pain behavior after plantar incision.

Methods

Rats with lumbar intrathecal catheters were anesthetized with halothane. Fifteen minutes before an incision was made, drug [40 nmol MK-801; 20 nmol NBQX; or 200 nmol (+)-MCPG] or vehicle was injected intrathecally followed by an infusion of the same drug for 75 min. Withdrawal thresholds to calibrated von Frey filaments applied adjacent to the wound and response frequencies to a blunt mechanical stimulus applied directly to the wound were measured before incision and 1, 2, 4, and 6 h after incision and then once daily for 6 days.

Results

Preincision treatments with antagonists against the NMDA (MK-801) and group I and II metabotropic receptors [(+)-MCPG] did not inhibit the development of mechanical hyperalgesia caused by incision. Preincision treatment with the non-NMDA receptor antagonist NBQX increased withdrawal thresholds at 1 and 2 h and on postoperative day 1 compared with the vehicle group; response frequencies were reduced 1 and 2 h after incision and on postoperative day 2 (P < 0.05). In an additional group, postincision treatment with NBQX was similar to preincision treatment.

Conclusion

Spinal NMDA and mGluR antagonists may not be useful for preventing postsurgical pain. Spinal non-NMDA receptor antagonists reduced pain behaviors, but a preventive effect using preincision treatment was not apparent.
Local Anesthetic Inhibition of m1 Muscarinic Acetylcholine Signaling
Authors: Hollmann Markus W. , Fischer Lars G. , Byford Anne M. , Durieux Marcel E.
Published: November 2003

Background

Local anesthetics inhibit lipid mediator signaling (lysophosphatidate, thromboxane) by acting on intracellular domains of the receptor or on the G protein. On receptors for polar agonists, the ligand-binding pocket could form an additional site of interaction, possibly resulting in superadditive inhibition. The authors therefore investigated the effects of local anesthetics on m1 muscarinic receptor functioning.

Methods

The authors expressed receptors in isolation using Xenopus oocytes. Using a two-electrode voltage clamp, the authors measured the effects of lidocaine, QX314 (permanently charged), and benzocaine (permanently uncharged) on Ca2+-activated Cl- currents elicited by methylcholine. The authors also characterized the interaction of lidocaine with [3H] quinuclydinyl benzylate ([3H]QNB) binding to m1 receptors.

Results

Lidocaine inhibited muscarinic signaling with a half-maximal inhibitory concentration (IC50 18 nm) 140-fold less than that of extracellularly administered QX314 (IC50 2.4 microm). Intracellularly injected QX314 (IC50 0.96 mm) and extracellularly applied benzocaine (IC50 1.2 mm) inhibited at high concentrations only. Inhibition of muscarinic signaling by extracellularly applied QX314 and lidocaine was the result of noncompetitive antagonism. Intracellularly injected QX314 and benzocaine inhibited muscarinic and lysophosphatidate signaling at similar concentrations, suggesting an action on the common G-protein pathway. Combined administration of intracellularly injected (IC50 19 microm) and extracellularly applied QX314 (IC50 49 nm) exerted superadditive inhibition. Lidocaine did not displace specific [3H]QNB binding to m1 receptors.

Conclusions

m1 Muscarinic signaling is inhibited by clinically relevant concentrations of lidocaine and by extracellularly administered QX314, suggesting that the major site of action is a extracellular domain of the muscarinic receptor. An additional less potent but superadditive inhibitory effect on the G-protein is suggested.
Process Analysis in Outpatient Knee Surgery
Authors: Williams Brian A. , Kentor Michael L. , Williams John P. , Figallo Chiara M. , Sigl Jeffrey C. , Anders Joel W. , Bear Taylor C. , Tullock William C. , Bennett Craig H. , Harner Christopher D. , Fu Freddie H.
Published: November 2003

Background

The performance of anesthetic procedures before operating room entry (e.g., with either general or regional anesthesia [RA] induction rooms) should decrease anesthesia-controlled time in the operating room. The authors retrospectively studied the associations between anesthesia techniques and anesthesia-controlled time, evaluating one surgeon performing a single procedure over a 3-yr period. The authors hypothesized that, using the anesthesia care team model, RA would be associated with reduced anesthesia-controlled time compared with general anesthesia (GA) alone or combined general-regional anesthesia (GA-RA).

Methods

The authors queried an institutional database for 369 consecutive patients undergoing the same procedure (anterior cruciate ligament reconstruction) performed by one surgeon over a 3-yr period (July 1995 through June 1998). Throughout the period of study, anesthesia staffing consisted of an attending anesthesiologist medically directing two nurse anesthetists in two operating rooms. Anesthesia-controlled time values were compared based on anesthesia techniques (GA, RA, or GA-RA) using one-way analysis of variance, general linear modeling using time-series and seasonal adjustments, and chi-square tests when appropriate. P < 0. 05 was considered significant.

Results

RA was associated with the lowest anesthesia-controlled time (11.4 +/- 1.3 min, mean +/- 2 SEM). GA-RA (15.7 +/- 1.0 min) was associated with lower anesthesia-controlled time than GA used alone (20.3 +/- 1.2 min).

Conclusions

When compared with GA without an induction room for outpatients undergoing anterior cruciate ligament reconstruction, RA with an induction room was associated with the lowest anesthesia- controlled time. Managers must weigh the costs and time required for anesthesiologists and additional personnel to place nerve blocks or induce GA preoperatively in such a staffing model.
Age Is Not an Impediment to Effective Use of Patient-controlled Analgesia by Surgical Patients
Authors: Gagliese Lucia , Jackson Marla , Ritvo Paul , Wowk Adarose , Katz Joel
Published: November 2003

Background

Obstacles to the use of patient-controlled analgesia (PCA) by elderly surgical patients have not been well-documented. Age differences in preoperative psychological factors, postoperative pain and analgesic consumption, treatment satisfaction, and concerns regarding PCA were measured to identify factors important to effective PCA use.

Methods

Preoperatively, young (mean age +/- SD, 39 +/- 9 yr; n = 45) and older (mean age +/- SD, 67 +/- 8 yr; n = 44) general surgery patients completed measures of attitudes toward and expectations of postoperative pain and PCA, psychological distress, health opinions, self-efficacy, and optimism. On the first 2 postoperative days, pain at rest and with movement and satisfaction with pain control were assessed using visual analog scales. Daily opioid intake was recorded. When PCA was discontinued, satisfaction and concerns about it were assessed.

Results

The older patients expected less intense pain (P </= 0.003) and preferred less information about (P </= 0.02) and involvement in (P </= 0.002) health care than young patients. There were no age differences with regard to pain at rest (P </= 0.22) or with movement (P </= 0.68). The older group self-administered less opioid than the young group (P </= 0.0001) and received PCA for more days than the young group (P </= 0.004). The groups did not differ in concerns about pain relief, adverse drug effects, including opioid addiction, and equipment use or malfunction. Satisfaction with PCA was high and did not differ between the groups.

Conclusions

Patient-controlled analgesia use was not hindered by age differences in beliefs about postoperative pain and opioids. Younger and older patients attained comparable levels of analgesia and were equally satisfied with their pain control.
Cerebral Hyperthermia in Children after Cardiopulmonary Bypass
Authors: Bissonnette Bruno , Holtby Helen M. , Davis Annette J. , Pua Hweeleng , Gilder Fay J. , Black Michael
Published: November 2003

Background

Cerebral hyperthermia after hypothermic cardiopulmonary bypass has been poorly documented for adults and never in children. This study was designed to monitor brain temperature during and up to 6 h after cardiopulmonary bypass in infants and children.

Methods

Fifteen infants and children, between 3 months and 6 yr of age, were studied. A right retrograde jugular bulb catheter was used to measure the jugular venous bulb temperature (JVBT) during the procedure and the first 6 h in the critical care unit. The temperature of the blood from the bypass machine was measured at the aorta through the cannula using an indwelling temperature probe. All data were acquired every minute.

Results

The age of the patients ranged from 3 to 71 months (median, 15 months). The mean weight was 11.5 +/- 8.4 kg. The mean JVBT recorded at the end of cardiopulmonary bypass was 36.9 +/- 1.4 degrees C but reached 39.6 +/- 0.8 degrees C after six h (P < 0.01). The kinetics of brain rewarming was determined by the slope of the mean JVBT and corresponded to y +/- 0.006x + 37.21 (r2 = 0.97). The JVBT differed from the tympanic temperature after 200 min (P < 0.01) and the lower esophageal (P < 0.05) and rectal (P < 0.001) temperatures after 300 min. After 6 h, the tympanic, rectal, and lower esophageal temperatures were 37.8 +/- 0.9, 37.7 +/- 0.6, and 38.4 +/- 0.7 degrees C, respectively, whereas the JVBT was 39.6 +/- 0.8 degrees C (P < 0.001). However, the correlation coefficients between the JVBT and the tympanic, rectal, and esophageal temperatures were 0.98, 0. 85, and 0.97, respectively. No complications were recorded with placement of the jugular bulb catheter.

Conclusions

Mean JVBT was significantly increased over the mean core temperature at all times from rewarming by cardiopulmonary bypass onward. Although the lower esophageal, rectal, and tympanic temperatures correlated well with JVBT, all three failed to reflect JVBT during recovery. This observation might help to elucidate factors involved in the functional and structural neurologic injury known to occur in pediatric patients.
Temporal Relation between Acoustic and Force Responses at the Adductor Pollicis during Nondepolarizing Neuromuscular Block
Authors: Bellemare François , Couture Jacques , Donati François , Plaud Benoît
Published: November 2003

Background

Contracting muscle emits sounds. The purpose of this study was to compare the time course of muscular paralysis at the adductor pollicis muscle (AP) with use of acoustic myography and mechanomyography.

Methods

Thirteen elective surgery patients, American Society of Anesthesiologists physical status I, received rocuronium (0.6 mg/kg intravenously) as a bolus dose during general anesthesia. Force of AP was measured with use of a strain gauge, and sounds were recorded simultaneously with use of a small condenser microphone fixed on the palmar surface of the hand over the AP. Supramaximal stimulation was applied to the ulnar nerve at 0.1 Hz for 45-60 min. In seven patients, the response to train-of-four stimulation was also recorded during recovery.

Results

Force and sounds both were equally sensitive in measuring maximum block. The relation between sound and force was curvilinear, with good agreement near 0 and 100% and acoustic response exceeding mechanical response at intermediate levels of block. The acoustic signal had a slower onset and a faster recovery than the force response. The fade response of sound to train-of-four stimulation also recovered faster than that of force.

Conclusion

Acoustic myography is an alternative method to monitor muscular paralysis that is easy to set up and applicable to most superficial muscles. However, the time course of relaxation at AP using acoustic myography differs from the time course of force relaxation. Therefore, these two methods are not equivalent when applied to AP.
Optimal Propofol Plasma Concentration during Upper Gastrointestinal Endoscopy in Young, Middle-aged, and Elderly Patients
Authors: Kazama Tomiei , Takeuchi Ken , Ikeda Kazuyuki , Ikeda Takehiko , Kikura Mutsuhito , Iida Takayuki , Suzuki Shuji , Hanai Hiroyuki , Sato Shigehito
Published: November 2003

Background

Suitable propofol plasma concentrations during gastroscopy have not been determined for suppressing somatic and hemodynamic responses in different age groups.

Methods

Propofol sedation at target plasma concentrations from 0.5 to 4.0 microgram/ml were performed randomly in three groups of patients (23 per group) who were undergoing elective outpatient gastroscopy: ages 17-49 yr (group 1), 50-69 yr (group 2), and 70-89 yr (group 3). Plasma propofol concentration in which 50% of patients do not respond to these different stimuli were determined by logistic regression: verbal command (Cp50ls), somatic response to gastroscopy (Cp50endo), and gag response to gastroscopy (Cp50gag). Hemodynamic responses were also investigated in the different age groups.

Results

Cp50ls concentrations were 2.23 microgram/ml (group 1), 1.75 microgram/ml (group 2), and 1.40 microgram/ml (group 3). The Cp50endo values in groups 1 and 2 were 2.87 and 2.34 microgram/ml, respectively, which were significantly higher than their respective Cp50ls values. Cp50endo value in group 3 was 1.64 microgram/ml, which was close to its Cp50ls value. Because of a high degree of interpatient variability, Cp50gag could not be defined. Systolic blood pressure response decreased with increasing propofol concentrations.

Conclusions

The authors determined the propofol concentration necessary for gastroscopy and showed that increasing age reduces it. Propofol concentration that suppresses somatic response induces loss of consciousness in almost all young patients.
Gender Affects Report of Pain and Function after Arthroscopic Anterior Cruciate Ligament Reconstruction
Authors: Taenzer Andreas H. , Clark Cantwell , Curry Craig S.
Published: November 2003

Background

Gender-related differences in pain have been clearly shown in experimental settings. Clinical studies of such differences have produced conflicting findings. No studies have shown a significant difference in pain experience associated with differences in functional outcomes. Arthroscopic anterior cruciate ligament reconstruction (AACLR) produces pain of moderate intensity and provides a useful setting for examining gender-related differences in pain and function.

Methods

This study was a retrospective review of prospectively gathered data collected for a continuous quality improvement program and involved all patients who underwent AACLR at a single outpatient facility since June 1992. Anesthetic, surgical, and perioperative management techniques were standardized. Using a questionnaire, all patients were routinely asked to record pain scores, narcotic consumption, and whether they were able to perform a standardized straight leg-raising maneuver on each of the first 5 postoperative days.

Results

A total of 736 patients were enrolled for surgery, 58% of whom completed the entire 5-day questionnaire. Women reported higher pain scores at rest as well as with activity on postoperative day 1 compared with men (P < 0.005). In addition, fewer women were able to perform the straight leg-raising maneuver on postoperative day 1 (P = 0.002) and postoperative day 2 (P = 0.004). There was no difference in the amount of narcotics consumed at any time during the study period.

Conclusions

Women seem to experience greater intensity of pain after AACLR that is associated with a decrease in an intermediate measure of functional outcome. These differences may result from differences in either response to analgesics or neuroprocessing.
Changes in Regional Myocardial Function after Coronary Artery Bypass Graft Surgery Are Predicted by Intraoperative Low-dose Dobutamine Echocardiography
Authors: Aronson Solomon , Dupont Frank , Savage Robert , Drum Melinda , Gunnar William , Jeevanandam Valluvan
Published: November 2003

Background

Left ventricular dysfunction is often reversed after coronary artery bypass graft (CABG) surgery; however, this change is not easily predicted. The authors hypothesized that functional changes after a low dose of dobutamine (5 microgram. kg-1. min-1) intraoperatively would predict functional changes when complete revascularization was achieved.

Methods

The authors analyzed 560 segments in 40 patients scheduled for elective CABG surgery for regional wall motion (1-5 scoring system) at four stages: baseline (after induction and intubation), with administration of low-dose dobutamine before cardiopulmonary bypass, after separation from cardiopulmonary bypass (early), and after administration of protamine (late). Two independent observers scored the myocardial regions according to a 16-segment model in multiple imaging planes. For each segment, the response to dobutamine was dichotomized as improved or not improved from baseline and analyzed with logistic regression. The influence of covariates (ejection fraction, myocardial infarction, diabetes mellitus, and beta blockers) was also determined with logistic regression models. P < 0.05 was considered significant.

Results

Changes in myocardial function after low-dose dobutamine were highly predictive for early (P < 0.0001) and late (P < 0.0001) changes in myocardial function from baseline regional scores. The overall odds ratio for early and late improvement increased by 20.7 and 34.6, respectively, when improvement was observed after low-dose dobutamine was administered. The overall positive predictive value of improved regional wall motion after CABG did not vary with left ventricular ejection fraction, a history of myocardial infarction, or beta blocker use, and it varied little with diabetic status (range, 0.86-0.96) if regional wall motion improved with low-dose dobutamine before CABG. The overall negative predictive value was 0.70; however, the range varied with diabetic status (i.e., lowest in diabetic patients and highest in nondiabetic patients).

Conclusion

Intraoperative low-dose dobutamine is a reliable method to predict myocardial functional reserve and to determine functional recovery expected after coronary revascularization.
Intracarotid Infusion of the Nitric Oxide Synthase Inhibitor, l-NMMA, Modestly Decreases Cerebral Blood Flow in Human Subjects
Authors: Joshi Shailendra , Young William L. , Duong D. Hoang , Ostapkovich Noeleen D. , Aagaard Beverly D. , Hashimoto Tomoki , Pile-Spellman John
Published: November 2003

Background

The authors hypothesized that if nitric oxide (NO) was a determinant of background cerebrovascular tone, intracarotid infusion of NG-monomethyl-L-arginine (L-NMMA), a NO synthase (NOS) inhibitor, would decrease cerebral blood flow (CBF) and intracarotid L-arginine would reverse its effect.

Methods

In angiographically normal cerebral hemispheres, after the initial dose-escalation studies (protocol 1), the authors determined the effect of intracarotid L-NMMA (50 mg/min for 5 min) on CBF and mean arterial pressure (MAP) over time (protocol 2). Changes in CBF and MAP were then determined at baseline, during L-NMMA infusion, and after L-NMMA during L-arginine infusion (protocol 3). To investigate effects of higher arterial blood concentrations of L-NMMA, changes in CBF and MAP were assessed at baseline and after a bolus dose of L-NMMA (250 mg/1 min), and vascular reactivity was tested by intracarotid verapamil (1 mg/min, protocol 4). CBF changes were also assessed during induced hypertension with intravenous phenylephrine (protocol 5).

Results

Infusion of L-NMMA (50 mg/min for 5 min, n = 7, protocol 2) increased MAP by 17% (86 +/- 8 to 100 +/- 11 mmHg; P < 0.0001) and decreased CBF by 20% (45 +/- 8 to 36 +/- 6 ml. 100 g-1. min-1; P < 0.005) for 10 min. Intracarotid l-arginine infusion after L-NMMA (protocol 3) reversed the effect of L-NMMA. Bolus L-NMMA (protocol 4) increased MAP by 20% (80 +/- 11 to 96+/-13 mmHg; P< 0.005), but there was no significant decrease in CBF. Intracarotid verapamil increased CBF by 41% (44+/- 8 to 62 +/- 9 ml. 100 g-1. min-1; P< 0.005). Phenylephrine-induced hypertension increased MAP by 20% (79 +/- 9 to 95 +/- 6 mmHg; P = 0.001) but did not affect CBF.

Conclusions

The results suggest that intracarotid L-NMMA modestly decreases CBF, and the background tone of cerebral resistance vessels may be relatively insensitive to NOS inhibition by the intraarterial route.
Potency of Bupivacaine Stereoisomers Tested In Vitro and In Vivo
Authors: Vladimirov Marina , Nau Carla , Mok Wai Man , Strichartz Gary
Published: November 2003

Background

Chiral local anesthetics, such as ropivacaine and levobupivacaine, have the potential advantage over racemic mixtures in showing reduced toxic side effects. However, these S-(levo, or "-")isomers also have reportedly lower potency than their optical antipode, possibly resulting in no advantage in therapeutic index. Potency for local anesthetics inhibiting Na+ channels or action potentials depends on the pattern of membrane potential and so also does the stereopotency ratio. Here the authors have quantitated the stereopotencies of R-, S-, and racemic bupivacaine, comparing several in vitro assays of neuronal Na+ channels with those from in vivo functional nerve block, to establish relative potencies and to understand better the role of different modes of channel inhibition in overall functional anesthesia.

Methods

The binding of bupivacaine to Na+ channels was assessed indirectly by its antagonism of [3H]-batrachotoxin binding to rat brain synaptosomes. Inhibition of Na+ currents by bupivacaine was directly assayed in voltage-clamped GH-3 neuroendocrine cells. Neurobehavioral functions were disrupted by bupivacaine percutaneously injected (0.1 ml; 0.0625-1.0%) at the rat sciatic nerve and semiquantitatively assayed. Concentration-dependent actions of R-, S-, and racemic bupivacaine were compared for their magnitude and duration of action.

Results

Competitive batrachotoxin displacement has a stereopotency ratio of R:S = 3:1. Inhibition of Na+ currents with different prepulse potentials shows that S > R potency when the membrane is hyperpolarized, and R > S potency when it is depolarized from normal resting values. Functional deficits assayed in vivo usually demonstrate no consistent enantioselectivity and only a modest stereopotency (R:S = 1.2-1.3) for peak analgesia achieved at the lowest doses. Other functions display no significant stereopotency in either the degree, the duration, or their product (area under the curve) at any dose.

Conclusion

Although the in vitro actions of bupivacaine showed stereoselectivity ratios of 1.3-3:1 (R:S), in vivo nerve block at clinically used concentrations showed much smaller ratios for peak effect and no significant enantioselectivity for duration. A primary role for the blockade of resting rather than open or inactivated Na+ channels may explain the modest stereoselectivity in vivo, although stereoselective factors controlling local disposition cannot be ruled out. Levo-(S-)bupivacaine is effectively equipotent to R- or racemic bupivacaine in vivo for rat sciatic nerve block.
Effects of Thiopental and Its Optical Isomers on Nicotinic Acetylcholine Receptors
Authors: Downie David L. , Franks Nicholas P. , Lieb William R.
Published: November 2003

Background

With the exception of gamma-aminobutyric acidA (GABAA) receptors, the major molecular targets underlying the anesthetizing actions of thiopental have yet to be established. Neuronal nicotinic acetylcholine receptors (nAChRs) are closely related to GABAA receptors and hence might also be major targets. If so, they might be expected to be substantially inhibited by surgical concentrations (EC50 = 25 micrometer) of thiopental and to display the same stereoselectivity as does general anesthesia.

Methods

Neuronal alpha4beta2, neuronal alpha7 and muscle alphabetagammadelta nAChRs were expressed in Xenopus oocytes. Peak acetylcholine-activated currents were measured at -70 mV using the two-electrode voltage clamp technique. Racemic thiopental and its two optical isomers were applied with and without preincubation and at high and low concentrations of acetylcholine.

Results

Inhibition of all three nAChRs was enhanced by preincubation with thiopental, a protocol that mimics the pharmacologic situation in vivo. Using this protocol, inhibition was further enhanced by high concentrations of acetylcholine, with IC50 = 18 +/- 2, 34 +/- 4, and 20 +/- 2 micrometer (mean +/- SEM) thiopental for the neuronal alpha4beta2, neuronal alpha7 and muscle alphabetagammadelta nAChRs, respectively, with Hill coefficients near unity. Neither the neuronal alpha7 nor the muscle alphabetagammadelta nAChR differentiated between the optical isomers of thiopental. However, R(+)-thiopental was significantly more effective than the S(-) isomer at inhibiting the neuronal alpha4beta2 nAChR; interestingly, this is diametrically opposite to their stereoselectivity for general anesthesia.

Conclusions

Both central neuronal and peripheral muscle nAChRs can be substantially inhibited by thiopental at surgical EC50 concentrations but with either no stereoselectivity or one opposite to that for general anesthesia. Thus, nAChRs are probably not crucial targets for producing thiopental anesthesia, although nAChRs may play a part in the side effects produced by this agent.
Cerebral Histopathology following Portal Venous Infusion of Bacteria in a Chronic Porcine Model
Authors: Bogdanski Ralph , Blobner Manfred , Becker Ingrid , Hänel Frank , Fink Heidrun , Kochs Eberhard
Published: November 2003

Background

The aim of this study was to histologically investigate brain damage after prolonged periods of bacteremia in pigs.

Methods

Twenty-one pathogen-free Göttingen minipigs were anesthetized and instrumented with a femoral arterial, a pulmonary arterial, and through midline abdominal incision with a portal venous catheter. After craniotomy the superior sagittal sinus was cannulated. A lumbosacral spinal catheter was inserted for sampling of cerebrospinal fluid. Twelve hours after instrumentation, the animals were randomized in two groups: septic and control animals. The septic group received an infusion of 107 colony-forming units per kilogram of living Escherichia coli over 0.5 h through portal venous catheter each day. The control group received saline. Postoperative intensive care treatment included 4 days of controlled mechanical ventilation, sedation, and intravenous nutrition. The brains then were removed, fixed, and processed for histology. Each pathologic alteration found in the samples was assessed and given a severity code (0-3).

Results

Sham-operated animals showed no alterations caused by the instrumentation and the intensive care treatment. The septic group showed typical clinical signs of sepsis. Vasopressor support and mechanical ventilation prevented systemic hypotension and hypoxemia. High serum and cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha were detected. The septic group showed severe histologic abnormalities of the brain including perivascular edema, spongiform degeneration, hyperemia, and purpura. Damage of neurons was seen including eosinophilic cytoplasm, shrunken nuclei, and disintegration of the nuclear membrane.

Conclusions

Abdominal sepsis induced severe brain damage that was not related to systemic hypoxia or ischemia. High cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-6 were related to an inflammatory process in the brain resulting in cerebral edema and death of neurons.