bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients with Malignant Hyperthermia Demonstrate an Altered Calcium Control Mechanism in B Lymphocytes
Authors: Sei Yoshitatsu , Brandom Barbara W. , Bina Saiid , Hosoi Eiji , Gallagher Kathleen L. , Wyre Hadley W. , Pudimat Paul A. , Holman Steve J. , Venzon David J. , Daly John W. , Muldoon Sheila
Published: November 2003

Background

Altered Ca2+ homeostasis in skeletal muscle is a key molecular event triggering malignant hyperthermia (MH) in malignant hyperthermia-susceptible (MHS) individuals. Genetic studies have shown that mutations in the type 1 ryanodine receptor (RYR1) are associated with MH susceptibility. Because human B lymphocytes express the RYR1, it is hypothesized that Ca2+ homeostasis in B lymphocytes is altered in MHS individuals.

Methods

This study investigated the Ca2+ response of B cells to caffeine and 4-chloro-m-cresol in 13 MHS and 21 MH-negative (MHN) individuals who had been diagnosed by caffeine halothane contracture test (CHCT) and 18 healthy volunteers. Changes in [Ca2+]i in B cells were measured directly in fluo-3 loaded cells using a dual-color flow cytometric technique. Further, B cell phenotype was correlated with CHCT results in a family with the Val2168Met (G6502A) mutation.

Results

Caffeine-induced (50 mm) increases in [Ca2+]i in B cells were significantly greater in MHS than in MHN (P = 0.0004), control (P = 0.0001) or non-MHS (MHN and control) individuals (P < 0.0001). The 4-chloro-m-cresol-induced (400 microm) increases in [Ca2+]i were also significantly different between MHS and controls (P = 0.003) or between MHS and non-MHS (MHN and control) individuals (P = 0.0078). A study of a family with the Val2168Met mutation demonstrated expression of the RYR1 mRNA mutant in B cells from the family members with MHS phenotype and a clear segregation of genotype with B-cell phenotype.

Conclusion

The Ca2+ responses to caffeine or 4-chloro-m-cresol in B lymphocytes showed significant differences between MHS and MHN (or control) individuals. Although the molecular mechanisms of these alterations are currently undetermined, the results suggest that the enhanced Ca2+ responses are associated with mutations in the RYR1 gene in some MHS individuals.
Comparative Efficacy of Acustimulation (ReliefBand®) versus Ondansetron (Zofran®) in Combination with Droperidol for Preventing Nausea and Vomiting
Authors: White Paul F. , Issioui Tijani , Hu Jie , Jones Stephanie B. , Coleman Jayne E. , Waddle Jean P. , Markowitz Scott D. , Coloma Margarita , Macaluso Amy R. , Ing Caleb H.
Published: November 2003

Background

Antiemetic drugs are costly, are associated with variable efficacy, and can produce unwanted side effects when used for prophylaxis against postoperative nausea and vomiting. This clinical study was designed to compare the efficacy of transcutaneous electrical acupoint stimulation using a ReliefBand to ondansetron (Zofran) when utilized alone or in combination for preventing postoperative nausea and vomiting after plastic surgery.

Methods

A single-center, randomized, double-blind, placebo- and sham-controlled study design was conducted to compare three prophylactic antiemetic treatment regimens in 120 outpatients undergoing plastic surgery procedures with routine low-dose droperidol prophylaxis: (1) ondansetron (n = 40), 4 mg intravenous ondansetron and a sham ReliefBand; (2) acustimulation (n = 40), 2 ml intravenous saline and an active ReliefBand; and (3) combination (n = 40), 4 mg intravenous ondansetron and an active ReliefBand. The incidences of postoperative nausea and vomiting, as well as the need for "rescue" antiemetics, were determined at specific time intervals for up to 72 h after surgery. The outcome variables assessed included recovery times, quality of recovery score, time to resumption of normal diet, and patient satisfaction with the prophylactic antiemetic therapy.

Results

Use of the ReliefBand in combination with ondansetron significantly reduced nausea (20 vs. 50%), vomiting (0 vs. 20%), and the need for rescue antiemetics (10 vs. 37%) compared with ondansetron alone at 24 h after surgery. Furthermore, the ability to resume a normal diet (74 vs. 35%) within 24 h after surgery was significantly improved when the ReliefBand was used to supplement ondansetron (vs. ondansetron alone). Finally, the quality of recovery (90 +/- 10 vs.70 +/- 20) and patient satisfaction (94 +/- 10 vs. 75 +/- 22) scores were significantly higher in the combination group the ondansetron group. There were no significant differences between the ReliefBand and ondansetron when administered as adjuvants to droperidol for antiemetic prophylaxis.

Conclusions

The ReliefBand compared favorably to ondansetron (4 mg intravenously) when used for prophylaxis against postoperative nausea and vomiting. Furthermore, the acustimulation device enhanced the antiemetic efficacy of ondansetron after plastic surgery.
Impact of Alloantigens and Storage-associated Factors on Stimulated Cytokine Response in an In Vitro Model of Blood Transfusion
Authors: Biedler Andreas E. , Schneider Sven O. , Seyfert Ullrich , Rensing Hauke , Grenner Sasha , Girndt Matthias , Bauer Inge , Bauer Michael
Published: November 2003

Background

Transfusion of blood may contribute to immunosuppression in major surgery. The authors assessed the impact of alloantigens and storage on function of peripheral blood mononuclear cells cultured in their physiologic environment.

Methods

Blood units (whole blood, packed erythrocytes) were prepared with or without prestorage leukodepletion and stored for 24-26 days. Blood samples were coincubated with allogeneic fresh blood, autologous, or allogeneic stored blood. Endotoxin-stimulated release of tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10) was measured after 24 h of culture by enzyme-linked immunosorbent assay.

Results

Coincubation with equal amounts of allogeneic fresh blood showed almost no influence on TNF-alpha (-12%, not significant) and IL-10 (+11%, not significant) release. Stored allogeneic whole blood resulted in a significant TNF-alpha depression (-61%) and IL-10 induction (+221%). These effects were diminished but not prevented by prestorage leukodepletion (TNF-alpha -42%, IL-10 +110%) and required the presence of soluble factors (TNF-alpha suppression) and cellular components (IL-10 induction). TNF-alpha decrease and IL-10 increase were in the same order of magnitude (-40%, +134% with, -65%, +314% without leukodepletion) after coincubation with autologous blood. In contrast, allogeneic erythrocytes had only little effects (TNF-alpha -6%, IL-10 +36%) even at this high transfusion equivalent.

Conclusion

These data suggest that banked whole blood has an immunosuppressive effect that is largely attributable to storage-dependent factors. These factors are partially removed by prestorage leukodepletion, while the contribution of alloantigens is of minor significance. Immunosuppressive effects are least apparent with leukodepleted erythrocytes, suggesting that the presence of plasma during storage is required for the immunosuppressive effect to develop.
Intravenous Magnesium Sulfate Administration Reduces Propofol Infusion Requirements during Maintenance of Propofol–N2O Anesthesia
Authors: Choi Jae Chan , Yoon Kyung Bong , Um Dae Ja , Kim Chan , Kim Jin Soo , Lee Sang Gyu
Published: November 2003

Background

The authors investigated whether an intravenous administration of magnesium sulfate reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia.

Methods

Part I study: 54 patients undergoing total abdominal hysterectomy were randomly divided into two groups (n = 27 per group). The patients in the control group received 0.9% sodium chloride solution, whereas the patients in the magnesium group received magnesium (50 mg/kg as a bolus, then 8 mg x kg(-1) x h(-1)). To maintain mean arterial blood pressure (MAP) and heart rate (HR) at baseline value, the propofol infusion rate was changed when the MAP or the HR changed. The amount of propofol infused excluding the bolus dosage was divided by patient's body weight and total infusion time. Part II study: Another 20 patients were randomly divided into two groups (n = 10 per group). When the MAP and HR had been maintained at baseline value and the propofol infusion rate had been maintained at 80 microg x kg(-1) x min(-1) (magnesium group) and 160 microg x kg(-1) x min(-1) (control group), bispectral index (BIS) values were measured.

Results

Part I: The mean propofol infusion rate in the magnesium group (81.81 +/- 13.09 microg x kg(-1) x min(-1)) was significantly less than in the control group (167.57 +/- 47.27). Part II: BIS values in the control group (40.70 +/- 3.89) were significantly less than those in the magnesium group (57.80 +/- 7.32).

Conclusion

Intravenous administration of magnesium sulfate reduces propofol infusion requirements. These results suggest that magnesium administration may have an effect on anesthesia or analgesia and may be a useful adjunct to propofol anesthesia.
Long-term Pain and Activity during Recovery from Major Thoracotomy Using Thoracic Epidural Analgesia
Authors: Ochroch E. Andrew , Gottschalk Allan , Augostides John , Carson Kathryn A. , Kent Laura , Malayaman Nini , Kaiser Larry R. , Aukburg Stanley J.
Published: November 2003

Background

Pain following thoracotomy can persist for years with an undetermined impact on quality of life. Factors hypothesized to modulate this painful experience include analgesic regimen, gender, and type of incision.

Methods

A total of 157 generally healthy patients of both genders scheduled for segmentectomy, lobectomy, or bilobectomy through a posterolateral or muscle-sparing incision were randomly assigned to receive thoracic epidural analgesia initiated prior to incision or at the time of rib approximation. Pain and activity scores were obtained 4, 8, 12, 24, 36, and 48 weeks after surgery.

Results

Overall, there were no differences in pain scores between the control and intervention groups during hospitalization (P >or= 0.165) or after discharge (P>or= 0.098). The number of patients reporting pain 1 yr following surgery (18 of 85; 21.2%) was not significantly different (P = 0.122) from the number reporting preoperative pain (15 of 120; 12.5%). During hospitalization, women reported greater pain than men (worst pain, P= 0.007; average pain, P= 0.016). Women experienced fewer supraventricular tachydysrhythmias (P = 0.013) and were thus discharged earlier (P = 0.002). After discharge women continued to report greater discomfort than men (P <or= 0.016), but did not differ from men in their level of physical activity (P = 0.241).

Conclusions

Initiation of thoracic epidural analgesia prior to incision or the use of a muscle-sparing incision did not significantly impact pain or physical activity. Although women reported significantly greater pain during hospitalization and after discharge, they experienced fewer complications, were more likely to be discharged from the hospital sooner, and were just as active after discharge as men.
Role of Prostaglandin Receptor EP1in the Spinal Dorsal Horn in Carrageenan-induced Inflammatory Pain
Authors: Nakayama Yoshito , Omote Keiichi , Namiki Akiyoshi
Published: November 2003

Background

Prostaglandin E2 (PGE2) and the receptor for PGE2 (EP receptor) are key factors contributing to the generation of hyperalgesia caused by inflammation. The current study was designed to investigate the roles of PGE2 and EP1 receptors in the spinal cord in the development and maintenance of inflammatory pain, using behavioral, microdialysis, and intracellular calcium ion concentration ([Ca2+]i) assays.

Methods

Inflammation was induced by an injection of carrageenan into the plantar surface of the rat hind paw. The effects of inflammation were evaluated at the time points of 3 h (early phase) and 15 h (late phase) after carrageenan injection. In behavioral assays, withdrawal thresholds to mechanical stimuli were evaluated. The effect of an intrathecally administered selective EP1 antagonist, ONO-8711, on the carrageenan-induced hyperalgesia was examined. Using a spinal microdialysis method, PGE2 concentration in the spinal dorsal horn was measured. In [Ca2+]i assays, we measured [Ca2+]i in the spinal dorsal horn in transverse spinal slices and examined the effects of pretreatment with ONO-8711. Sensitivities of the changes in [Ca2+]i to PGE2 perfusion were also assessed.

Results

Mechanical hyperalgesia and paw edema were observed in both the early and late phases. The hyperalgesia was inhibited by intrathecal ONO-8711 in the late, but not early, phase. The concentration of PGE2 in the spinal dorsal horn increased in the late phase. The [Ca2+]i in the dorsal horn increased on the ipsilateral side to the inflammation in the late, but not early phase. This increase was suppressed by the pretreatment with ONO-8711. Magnitude of the increase in [Ca2+]i on the ipsilateral side in response to PGE2 perfusion was greater in the late phase than in the early phase.

Conclusion

The results suggested that activation of spinal EP1 receptors was crucial in the carrageenan-induced mechanical hyperalgesia in the late phase. It seems that some of the mechanisms underlying inflammation-induced plastic changes are mediated by time-dependent increase in PGE2 concentration, activation of EP1 receptors, and increase in [Ca2+]i in the spinal dorsal horn.
Gabapentin and Pregabalin Can Interact Synergistically with Naproxen to Produce Antihyperalgesia
Authors: Hurley Robert W. , Chatterjea Debika , Rose Feng Meihua , Taylor Charles P. , Hammond Donna L.
Published: November 2003

Background

Gabapentin and pregabalin are anticonvulsants with antihyperalgesic effects in animal models of neuropathic and inflammatory nociception. This study characterized the manner in which gabapentin or pregabalin interacts with naproxen to suppress thermal hyperalgesia and inflammation in the carrageenan model of peripheral inflammation.

Methods

Gabapentin, pregabalin, naproxen, or a fixed-dose ratio of gabapentin + naproxen or pregabalin + naproxen was administered orally to rats after the induction of inflammation by intraplantar injection of lambda-carrageenan in one hind paw. Nociceptive thresholds were determined by the radiant heat paw-withdrawal test. Paw edema was measured by plethysmometry. Drug plasma concentrations were determined by a liquid chromatography-mass spectroscopy-mass spectroscopy method.

Results

Gabapentin, pregabalin, and naproxen alone reversed thermal hyperalgesia with ED50 values of 19.2, 6.0, and 0.5 mg/kg, respectively. Mixtures of gabapentin + naproxen in fixed-dose ratios of 50:1, 10:1, or 1:1 interacted synergistically to reverse carrageenan-induced thermal hyperalgesia. However, 1:50 gabapentin + naproxen produced only additive effects. No combination of gabapentin + naproxen decreased paw edema in a manner greater than additive. Plasma concentrations of gabapentin and naproxen were unaltered by the addition of the other drug. The mixture of 10:1 of pregabalin + naproxen interacted synergistically to reverse thermal hyperalgesia on the inflamed hind paw, whereas mixtures of 1:1 or 1:10 produced additive effects.

Conclusions

These data suggest that gabapentin + naproxen and pregabalin + naproxen can interact synergistically or additively to reverse thermal hyperalgesia associated with peripheral inflammation. Therefore, the use of gabapentin or pregabalin in low-dose combinations with naproxen may afford therapeutic advantages for clinical treatment of persistent inflammatory pain.
Major Complications of Regional Anesthesia in France
Authors: Auroy Yves , Benhamou Dan , Bargues Laurent , Ecoffey Claude , Falissard Bruno , Mercier Frédéric , Bouaziz Hervé , Samii Kamran
Published: November 2003

Background

Several previous surveys have estimated the rate of major complications that occur after regional anesthesia. However, because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques, reappraisal of the incidence and the characteristics of major complications is useful.

Methods

All French anesthesiologists were invited to participate in this 10-month prospective survey based on (1) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts, and (2) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets. The service was free of charge for participants.

Results

The participants (n = 487) reported 56 major complications in 158,083 regional anesthesia procedures performed (3.5/10,000). Four deaths were reported. Cardiac arrest occurred after spinal anesthesia (n = 10; 2.7/10,000) and posterior lumbar plexus block (n = 1; 80/10,000). Systemic local anesthetic toxicity consisted of seizures only, without cardiac toxicity. Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia (14.4/10,000 vs. 2.2/10,000). Most neurologic complications were transient. Among 12 that occurred after peripheral nerve blocks, 9 occurred in patients in whom a nerve stimulator had been used.

Conclusion

This prospective survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications.
Antiemetic Prophylaxis for Office-based Surgery
Authors: Tang Jun , Chen Xiaoguang , White Paul F. , Wender Ronald H. , Ma Hong , Sloninsky Alexander , Naruse Robert , Kariger Robert , Webb Tom , Zaentz Alan
Published: November 2003

Background

Office-based surgery has become increasingly popular because of its cost-saving potential. However, the occurrence of postoperative nausea and vomiting (PONV) can delay patient discharge. Prophylaxis using a combination of antiemetic drugs has been suggested as an effective strategy for minimizing PONV. The authors designed this randomized, double-blinded, placebo-controlled study to assess the efficacy of ondansetron and dolasetron when administered in combination with droperidol and dexamethasone for routine antiemetic prophylaxis against PONV in the office-based surgery setting.

Methods

Following institutional review board approval, 135 consenting outpatients with American Society of Anesthesiologists physical status I-III who were undergoing superficial surgical procedures lasting 20-40 min were randomly assigned to one of three antiemetic treatment groups. Propofol was administered for induction of anesthesia, followed by 2-4% desflurane with 67% nitrous oxide in oxygen. Desflurane was subsequently adjusted to maintain a clinically adequate depth of anesthesia with an electroencephalographic Bispectral Index value between 50 and 60. All patients received 0.625 mg intravenous droperidol and 4 mg intravenous dexamethasone after induction of anesthesia. The study medication, containing normal saline (control), 12.5 mg intravenous dolasetron, or 4 mg intravenous ondansetron, was administered prior to the end of surgery. All patients received local anesthetics at the incisional site and 30 mg intravenous ketolorac to minimize postoperative pain. Recovery profiles, incidence of PONV, requirement for rescue antiemetic drugs, complete response rates, and patient satisfaction were assessed.

Results

The recovery times to patient orientation, oral intake, ambulation, and actual discharge did not differ among the three groups. The incidence of PONV, nausea scores, and requirement for rescue antiemetics were also similar in all three groups during the 24-h study period. In addition, the complete response rates to the prophylactic antiemetics (96-98%) and percentages of very satisfied patients (93-98%) were equally high in all three groups. However, the antiemetic drug acquisition costs were US $2.50, $15.50, and $18.50 in the control, dolasetron, and ondansetron groups, respectively.

Conclusion

The addition of dolasetron (12.5 mg) or ondansetron (4 mg) failed to improve the antiemetic efficacy of droperidol (0.625 mg intravenous) and dexamethasone (4 mg intravenous) when they were used for routine prophylaxis in the office-based surgery setting.
Effects of EDTA- and Sulfite-containing Formulations of Propofol on Respiratory System Resistance after Tracheal Intubation in Smokers
Authors: Rieschke Petra , LaFleur Bonnie J , Janicki Piotr K.
Published: November 2003

Background

The formulation of sulfite-containing propofol (SCP) has not been thoroughly investigated in patients with the extensive smoking history for the effects on the total respiratory system resistance after tracheal intubation. However adverse effects, including acute asthma and bronchospasm, have been reported with several other parenteral formulations of drugs containing sulfite as preservative. Therefore, the aim of this prospective randomized and double blind study was to investigate the effects of EDTA-containing propofol (ECP) and SCP on total respiratory system resistance (Rrs) in patients with the prolonged smoking history and undergoing propofol-based total intravenous anesthesia with tracheal intubation.

Methods

40 patients scheduled for general anesthesia were enrolled into the study. Anesthesia was induced with either 2 mg/kg ECP, or 2 mg/kg SCP followed by vecuronium (0.1 mg/kg) to ensure complete neuromuscular relaxation for the time of the study. Maintenance anesthesia was continued with propofol infusion at 0.15 mg/kg/min for the first 15 min after intubation. Total respiratory system resistance (Rrs), was measured continuously for 10 min postintubation.

Results

The analysis of repeated Rrs measurements taken every minute for 10 min postintubation revealed trend consisting of higher Rrs in the SCP group when compared to the ECP group. The statistical analysis of the data performed using repeated measures analysis of covariance demonstrated statistically significant effect (P < 0.05) of the treatment group factor (SCP vs. ECP) and the time factor (time after intubation) on the postintubation Rrs.

Conclusion

The total respiratory system resistance measured repeatedly for 10 min after tracheal intubation in patients with smoking history is significantly elevated after induction with SCP than after induction with ECP. The preservative used for propofol formulation may alter the effects of propofol on the total respiratory system resistance in smokers.
Antifibrinolytic Therapy and Perioperative Blood Loss in Cancer Patients Undergoing Major Orthopedic Surgery
Authors: Amar David , Grant Florence M. , Zhang Hao , Boland Patrick J. , Leung Denis H. , Healey John A.
Published: November 2003

Background

Aprotinin has been reported to reduce blood loss and transfusion requirements in patients having major orthopedic operations. Data on whether epsilon amino-caproic acid (EACA) is effective in this population are sparse.

Methods

Sixty-nine adults with malignancy scheduled for either pelvic, extremity or spine surgery during general anesthesia entered this randomized, double-blind, placebo-controlled trial, and received either intravenous aprotinin (n = 23), bolus of 2 x 10(6) kallikrein inactivator units (KIU), followed by an infusion of 5 x 10(5) KIU/h, or EACA (n = 22), bolus of 150 mg/kg, followed by a 15 mg/kg/h infusion or saline placebo (n = 24) during surgery. Our goal was to determine whether prophylactic EACA or aprotinin therapy would reduce perioperative blood loss (intraoperative + first 48h) >30% when compared to placebo.

Results

The mean age of the study population was 52 +/- 17 yr. The groups did not differ in age, duration of surgery, perioperative blood loss or number of packed erythrocyte units transfused. When compared to the placebo group, the two treated groups had a significantly lower D-Dimer level immediately after surgery, P < 0.01.

Conclusions

Under the conditions of this study, we were unable to find a clinical benefit to using aprotinin or EACA to reduce perioperative blood loss or transfusion requirements during major orthopedic surgery in cancer patients.
Phonomyography as a Novel Method to Determine Neuromuscular Blockade at the Laryngeal Adductor Muscles
Authors: Hemmerling Thomas M. , Babin Denis , Donati François
Published: November 2003

Background

Neuromuscular blockade at the laryngeal adductor muscles may be measured using the cuff of a endotracheal tube placed between the vocal cords. Phonomyography is an alternative method of neuromuscular monitoring. In this study, phonomyography is applied to determine blockade at the larynx and compared with the cuff pressure method.

Methods

After the authors obtained approval from the ethics committee and informed consent, 28 patients were entered in the study. After induction of anesthesia, a endotracheal tube was inserted. Its cuff was placed in the trachea in routine fashion (n = 14) or between the vocal cords (n = 14). In all patients, a small condenser microphone was placed in the vestibular fold, just lateral to the tube, next to the laryngeal adductor muscles. The recurrent laryngeal nerve was stimulated supramaximally with single twitch stimulation (0.1 Hz) for onset, and train-of-four stimulation every 12 s during offset of neuromuscular blockade was produced by 0.1 mg/kg mivacurium. Onset and recovery of neuromuscular blockade measured by the two methods were compared using the test (P < 0.05), and a Bland-Altman test was performed to define agreement between the two methods. Onset and recovery of neuromuscular blockade measured by phonomyography with the cuff placed between the vocal cords or in the trachea were compared using the test (P < 0.05).

Results

Mean onset, maximum effect, and time to reach 25% and 75% of control twitch response for phonomyography cuff pressure method were 145 s (SD, 25) 156 s (SD, 33), 89% (SD, 4) 91% (SD, 4), 9 min (SD, 4) 10 min (SD, 3), and 27 min (SD, 4) 29 min (SD, 4), respectively, without being significantly different. Mean bias was -2%, with limits of agreement of -20 and +18% for all signals (cuff method minus phonomyography). There was no significant difference in onset and offset of neuromuscular blockade measured using phonomyography with the cuff placed between the vocal cords or in the trachea.

Conclusions

Both methods can be used interchangeably to determine neuromuscular blockade of the laryngeal adductor muscles. Phonomyography allows measurement of laryngeal blockade with the endotracheal tube in the normal position.
Isoflurane Alters Energy Substrate Metabolism to Preserve Mechanical Function in Isolated Rat Hearts following Prolonged No-Flow Hypothermic Storage
Authors: Finegan Barry A. , Gandhi Manoj , Cohen Matthew R. , Legatt Donald , Clanachan Alexander S.
Published: November 2003

Background

Isoflurane enhances mechanical function in hearts subject to normothermic global or regional ischemia. The authors examined the effectiveness of isoflurane in preserving mechanical function in hearts subjected to cardioplegic arrest and prolonged hypothermic no-flow storage. The role of isoflurane in altering myocardial glucose metabolism during storage and reperfusion during these conditions and the contribution of adenosine triphosphate-sensitive potassium (K(atp)) channel activation in mediating the functional and metabolic effects of isoflurane preconditioning was determined.

Methods

Isolated working rat hearts were subjected to cardioplegic arrest with St. Thomas' II solution, hypothermic no-flow storage for 8 h, and subsequent aerobic reperfusion. The consequences of isoflurane treatment were assessed during the following conditions: (1) isoflurane exposure before and during storage; (2) brief isoflurane exposure during early nonworking poststorage reperfusion; and (3) isoflurane preconditioning before storage. The selective mitochondrial and sarcolemmal K(atp) channel antagonists, 5-hydroxydecanoate and HMR 1098, respectively, were used to assess the role of K(atp) channel activation on glycogen consumption during storage in isoflurane-preconditioned hearts.

Results

Isoflurane enhanced recovery of mechanical function if present before and during storage. Isoflurane preconditioning was also protective. Isoflurane reduced glycogen consumption during storage under the aforementioned circumstances. Storage of isoflurane-preconditioned hearts in the presence of 5-hydroxydecanoate prevented the reduction in glycogen consumption during storage and abolished the beneficial effect of isoflurane preconditioning on recovery of mechanical function.

Conclusions

Isoflurane provides additive protection of hearts subject to cardioplegic arrest and prolonged hypothermic no-flow storage and favorably alters energy substrate metabolism by modulating glycolysis during ischemia. The effects of isoflurane preconditioning on glycolysis during hypothermic no-flow storage appears to be associated with activation of mitochondrial K(atp) channels.
Preconditioning with Sevoflurane Reduces Changes in Nicotinamide Adenine Dinucleotide during Ischemia–Reperfusion in Isolated Hearts
Authors: Riess Matthias L. , Novalija Enis , Camara Amadou K. S. , Eells Janis T. , Chen Qun , Stowe David F.
Published: November 2003

Background

Ischemia causes an imbalance in mitochondrial metabolism and accumulation of nicotinamide adenine dinucleotide (NADH). We showed that anesthetic preconditioning (APC), like ischemic preconditioning, improved mitochondrial NADH energy balance during ischemia and improved function and reduced infarct size on reperfusion. Opening adenosine triphosphate-sensitive potassium (K(atp)) channels may be involved in triggering APC. The authors tested if effects of APC on NADH concentrations before, during, and after ischemia are reversible by 5-hydroxydecanoate (5-HD), a putative mitochondrial K channel blocker.

Methods

Nicotinamide adenine dinucleotide fluorescence was measured in 60 guinea pig Langendorff-prepared hearts assigned into five groups: (1) no treatment before ischemia; (2) APC by exposure to 1.3 mm sevoflurane for 15 min; (3) 200 microm 5-HD from 5 min before to 15 min after sevoflurane exposure; (4) 35 min 5-HD alone; and (5) no treatment and no ischemia. Sevoflurane was washed out for 30 min, and 5-HD for 15 min, before 30-min ischemia and 120-min reperfusion.

Results

Nicotinamide adenine dinucleotide was reversibly increased during sevoflurane exposure before ischemia, and the increase and rate of decline in NADH during ischemia were reduced after APC. 5-HD abolished these changes in NADH. On reperfusion, function was improved and infarct size reduced after APC compared with other groups.

Conclusion

Anesthetic preconditioning was evidenced by improved mitochondrial bioenergetics as assessed from NADH concentrations during ischemia and by attenuated reperfusion injury. Reversal of APC by bracketing sevoflurane exposure with 5-HD suggests that APC is triggered by mitochondrial K channel opening or, alternatively, by attenuated mitochondrial respiration without direct involvement of mitochondrial K channel opening.
Antinociceptive Effect of Low-Dose Intrathecal Neostigmine Combined with Intrathecal Morphine following Gynecologic Surgery
Authors: Almeida Raquel A. , Lauretti Gabriela R. , Mattos Anita L.
Published: November 2003

Background

The purpose of this study was to determine whether combination of 1-5 microg intrathecal neostigmine would enhance analgesia from a fixed intrathecal dose of morphine.

Methods

A total of 60 patients undergoing gynecologic surgery were randomized to one of five groups. Patients received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline, 100 microg morphine, or 1-5 microg neostigmine). The control group received spinal saline as the test drug. The morphine group received spinal morphine as test drug. The morphine + 1 microg neostigmine group received spinal morphine and 1 microg neostigmine. The morphine + 2.5 microg neostigmine group received spinal morphine and 2.5 microg neostigmine. Finally, the morphine + 5 microg neostigmine group received spinal morphine and 5 microg neostigmine.

Results

The groups were demographically similar. The time to first rescue analgesic (minutes) was longer for all patients who received intrathecal morphine combined with 1-5 microg neostigmine (median, 6 h) compared with the control group (median, 3 h) (P < 0.02). The morphine group (P < 0.05) and the groups that received the combination of 100 microg intrathecal morphine combined with neostigmine (P < 0.005) required less rescue analgesics in 24 h compared with the control group. The incidence of perioperative adverse effects was similar among groups (P > 0.05).

Conclusions

The addition of 1-5 microg spinal neostigmine to 100 microg morphine doubled the duration to first rescue analgesic in the population studied and decreased the analgesic consumption in 24 h, without increasing the incidence of adverse effects. The data suggest that low-dose spinal neostigmine may improve morphine analgesia.
High Spinal Anesthesia for Cardiac Surgery
Authors: Lee Trevor W. R. , Grocott Hilary P. , Schwinn Debra , Jacobsohn Eric
Published: November 2003

Background

This double-blind, randomized, controlled trial examined the effect of high-dose intrathecal bupivacaine in combination with general anesthesia on atrial beta-adrenergic receptor function, the stress response, and hemodynamics during coronary artery bypass graft surgery.

Methods

Thirty-eight patients were randomized to either control (n = 19) or intrathecal bupivacaine (ITB) groups (n = 19). Patients in the ITB group received 37.5 mg intrathecal hyperbaric bupivacaine before induction of general anesthesia. Control patients received an injection of local anesthetic into the skin and subcutaneous tissues (sham spinal). Comparisons were made between groups with respect to atrial receptor desensitization and down-regulation, in addition to circulating catecholamines and hemodynamics.

Results

In patients with cardiopulmonary bypass (CPB) times in excess of 1 h, the ITB group had significantly less atrial beta-receptor dysfunction, as measured by maximal isproteronol, 50% maximal isoproterenol, sodium fluoride-stimulated activity, and zinterol stimulation assays of adenylyl cyclase activity (P < or = 0.02) and beta-adrenergic receptor density (P = 0.02). Serum epinephrine, norepinephrine, and cortisol concentrations were significantly lower in the ITB group, independent of CPB times (P < 0.0001, P < 0.001, and P < 0.05, respectively). ITB patients had a higher cardiac index and a lower pulmonary vascular resistance index in the post-CPB time period (P < 0.01 and P < 0.05, respectively). In the pre-CPB period, mean arterial pressure and systemic vascular resistance index were significantly lower in the ITB group.

Conclusions

High-dose intrathecal bupivacaine, when combined with general anesthesia, resulted in less beta-receptor dysfunction and a lower stress response during coronary artery bypass graft surgery.
Indocyanine Green
Authors: Dietz Friederike B. , Jaffe Richard A.
Published: November 2003

Background

The inadvertent intravascular injection of a local anesthetic during epidural anesthesia is an uncommon but potentially serious complication. Epinephrine, the most commonly used marker, does not provide sufficient sensitivity to exclude intravascular injection in all patient populations. The dye indocyanine green (ICG) has been proposed as an alternative marker. It has been demonstrated that ICG could be used to detect intravascular injections with a simple transcutaneous spectrophotometric technique. Although the safety of intravenous ICG is well documented, its neurotoxic potential requires careful study given the probability of inadvertent intrathecal injection during test injections used to verify epidural catheter placement.

Methods

In this study, the authors investigated the neurophysiologic effects of clinically relevant concentrations of ICG (range, 28.6-286 microm) on single myelinated and unmyelinated dorsal root axons in rats by measuring effects on impulse generation and conduction.

Results

In contrast to the apparent absence of toxicity when injected intravenously, ICG applied to intact dorsal roots at concentrations likely to be encountered with an epidural test dose produced long-lasting conduction block (21 of 26 axons) or spontaneous bursting activity (7 of 26 axons) in myelinated and unmyelinated dorsal root axons.

Conclusion

Given this apparent neurotoxicity, ICG should not be used when intrathecal or nerve root injection is possible.
Activation of Peripheral Excitatory Amino Acid Receptors Decreases the Duration of Local Anesthesia
Authors: Cairns Brian E. , Gambarota Giulio , Dunning Patricia S. , Mulkern Robert V. , Berde Charles B.
Published: November 2003

Background

Postsurgical wound infiltration with the -methyl-d-aspartate receptor antagonist ketamine and bupivacaine can significantly prolong the duration of local anesthesia. One possible mechanism for this effect is that increased glutamate concentrations, caused by tissue damage, sensitize nociceptive primary afferent fibers through activation of peripheral excitatory amino acid receptors.

Methods

The effect of intramuscular injection of hyper-tonic glutamate (1,000 mm), dextrose (1,400 mm), glutamate (1,000 mm) with the broad spectrum excitatory amino acid receptor antagonist kynurenate (100 mm), or isotonic saline (155 mm) on the duration of masseter muscle afferent fiber blockade after lidocaine (37 mm [1%], 10 microl) infiltration, on muscle edema formation and on muscle blood flow was examined.

Results

Injection of either glutamate or dextrose significantly shortened the duration of lidocaine blocks compared with isotonic saline; however, block duration was significantly shorter after glutamate than after dextrose. Injection of glutamate, but not isotonic saline, dextrose, or glutamate with kynurenate, significantly decreased the mechanical threshold of muscle afferent fibers. Injection of glutamate, dextrose, or glutamate with kynurenate produced equivalent large, long-lasting (> 60 min) edemas with high initial peak extracellular water content. Peak extracellular water decreased more rapidly when kynurenate was coinjected with glutamate. Both glutamate and dextrose significantly increased muscle blood flow for 30 min after injection. Glutamate-induced increases in blood flow were attenuated by kynurenate.

Conclusions

These results suggest that shortened lidocaine block durations observed after glutamate injection into the masseter muscle result from sensitization of afferent fibers as well as increases of peak extracellular water content and blood flow in masseter muscle. These effects of glutamate are mediated in part through activation of peripheral excitatory amino acid receptors.
Do They Understand? (Part II)
Authors: Tait Alan R. , Voepel-Lewis Terri , Malviya Shobha
Published: November 2003

Background

Participation of children in clinical research requires not only parental permission but also the assent of the child. Although there is no fixed age at which assent should be sought, investigators should obtain assent from children considered able to provide it. This study was designed to determine children's understanding of the elements of disclosure for studies in which they had assented to participate.

Methods

The study population included 102 children aged 7-18 yr who had given their assent to participate in a clinical anesthesia or surgical study. Children were interviewed using a semistructured format to determine their understanding of eight core elements of disclosure for the study to which they had agreed to participate. Two independent assessors scored the children's levels of understanding of these elements.

Results

The children's perceived level of understanding of the elements of disclosure was significantly greater than their measured understanding (7.0 +/- 2.4 vs 5.3 +/- 2.7, 0-10 scale; P< 0.0001). Complete understanding of the elements of disclosure for all children ranged from 30.4 to 89.4%. Children aged more than 11 yr had significantly greater understanding compared with younger children, particularly with respect to understanding of the study protocol, the benefits, and the freedom to withdraw.

Conclusions

Children approached for their assent to participate in a clinical anesthesia or surgery study have limited understanding of the elements of disclosure and their role as a research participant, particularly if they are aged less than 11 yr.
Correlation of Approximate Entropy, Bispectral Index, and Spectral Edge Frequency 95 (SEF95) with Clinical Signs of “Anesthetic Depth” during Coadministration of Propofol and Remifentanil
Authors: Bruhn Jörgen , Bouillon Thomas W. , Radulescu Lucian , Hoeft Andreas , Bertaccini Edward , Shafer Steven L.
Published: November 2003

Background

Several studies relating electroencephalogram parameter values to clinical endpoints using a single (mostly hypnotic) drug at relatively low levels of central nervous system depression (sedation) have been published. However, the usefulness of a parameter derived from the electroencephalogram for clinical anesthesia largely depends on its ability to predict the response to stimuli of different intensity or painfulness under a combination of a hypnotic and an (opioid) analgesic. This study was designed to evaluate the predictive performance of spectral edge frequency 95 (SEF95), BIS, and approximate entropy for the response to increasingly intense stimuli under different concentrations of both propofol and remifentanil in the therapeutic range.

Methods

Ten healthy male and ten healthy female volunteers were studied during coadministration of propofol and remifentanil. After having maintained a specific target concentration for 10 min, the depth of sedation-anesthesia was assessed using the responsiveness component of the Observer's Assessment of Alertness/Sedation (OAA/S) rating scale, which was modified by adding insertion of a laryngeal mask and laryngoscopy. The electroencephalogram derived parameters approximate entropy, bispectral index, and SEF95 were recorded just before sedation level was assessed.

Results

The prediction probability values for approximate entropy were slightly, but not significantly, better than those for bispectral index, SEF95, and the combination of drug concentrations. A much lower prediction ability was observed for tolerance of airway manipulation than for hypnotic endpoints.

Conclusion

Approximate entropy revealed informations on hypnotic and analgesic endpoints using coadministration of propofol and remifentanil comparable to bispectral index, SEF95, and the combination of drug concentrations.
Risk Factors for Adverse Postoperative Outcomes in Children Presenting for Cardiac Surgery with Upper Respiratory Tract Infections
Authors: Malviya Shobha , Voepel-Lewis Terri , Siewert Monica , Pandit Uma A. , Riegger Lori Q. , Tait Alan R.
Published: November 2003

Background

Otherwise healthy children who present for elective surgery with an upper respiratory infection (URI) may be at risk for perioperative respiratory complications. This risk may be increased in children with congenital heart disease who undergo cardiac surgery while harboring a URI because of their compromised cardiopulmonary status. Therefore, this study was designed to determine the incidence of peri- and postoperative complications in children undergoing cardiac surgery while harboring a URI.

Methods

The study population consisted of 713 children scheduled to undergo cardiac surgery. Of these, 96 had symptoms of URI, and 617 were asymptomatic. Children were followed prospectively from induction of anesthesia to discharge from the hospital to determine the incidence of postoperative respiratory, cardiovascular, neurologic, and surgical adverse events. Duration of postoperative ventilation, time in the intensive care unit (ICU), and length of hospital stay were also recorded.

Results

Children with URIs had a significantly higher incidence of respiratory and multiple postoperative complications than children with no URIs (29.2 vs 17.3% and 25 vs 10.3%, respectively; P< 0.01) and a higher incidence of postoperative bacterial infections (5.2 vs 1.0%; P= 0.01). Furthermore, logistic regression indicated that the presence of a URI was an independent risk factor for multiple postoperative complications and postoperative infections in children undergoing open heart surgery. Children with URIs also stayed longer in the intensive care unit than children with no URIs (75.9 +/- 89.8 h vs 57.7 +/- 63.8, respectively; P< 0.01). However, the overall length of hospital stay was not significantly different (8.4 vs 7.8 days, URI vs non-URI groups; P> 0.05).

Conclusions

The presence of a URI was predictive of postoperative infection and multiple complications in children presenting for cardiac surgery. Despite this, the presence of a URI does not appear to affect the patient's overall length of hospital stay nor the development of long-term sequelae.
Combined Effects of Nitrous Oxide and Propofol on the Dynamic Cerebrovascular Response to Step Changes in End-tidal Pco2in Humans
Authors: Inaba Shin , Sato Jiro , Aono Mitsuo , Numata Tsutomu , Nishino Takashi
Published: November 2003

Background

Nitrous oxide (N2O) and propofol exhibit directionally opposite effects on the cerebral circulation, vasodilation and vasoconstriction, respectively. The authors investigated an interaction between the two anesthetic agents on the dynamic cerebrovascular response to step changes in end-tidal pressure of carbon dioxide (PetCO2) in humans.

Methods

Participants with no systemic diseases were allocated into two groups, each of which was anesthetized sequentially with two protocols. Patients in group 1 were anesthetized with 30% O2 + 70% N2O. A continuous intravenous infusion of propofol (7-10 mg x kg(-1) x h(-1)) was then added to the N2O. Patients in group 2 were anesthetized first with continuous infusion of propofol (10 mg x kg(-1) h(-1)), and then 30% O2 + 70% N2O was added to the propofol anesthesia. Using transcranial Doppler ultrasonography, blood flow velocity at the middle cerebral artery (FV(MCA)) was measured during a step increase (on-response) followed by a step decrease (off-response) in PetCO2, with PetCO2 ranging between approximately 28 and 50 mmHg. The dynamic FV(MCA)-PetCO2 relationship was analyzed using a mathematical model that was characterized with a pure time delay, and a time constant and a gain each for the on- or off-response.

Results

The addition of propofol to the N2O anesthesia increased the on-response time constant (P < 0.01), whereas the addition of N2O to the propofol anesthesia increased the time constants for on- (P < 0.01) and off-responses (P < 0.05). However, the addition of either anesthetic did not affect the gains.

Conclusions

Propofol and N2O, when one is added to the other, produce similar dynamic FV(MCA) responses to sudden changes in PetCO2. Addition of each anesthetic slows the dynamic response and produces the response whose magnitude is proportional to the baseline FV(MCA).