bluuebunny/crossref_metadata_2025 huggingface dataset:
Transdermal Nitroglycerine Enhances Spinal Sufentanil Postoperative Analgesia following Orthopedic Surgery
Authors: Lauretti Gabriela R. , de Oliveira Raquel , Reis Marlene P. , Mattos Anita L. , Pereira Newton L.
Published: November 2003

Background

Sufentanil is a potent but short-acting spinal analgesic used to manage perioperative pain. This study evaluated the influence of transdermal nitroglycerine on the analgesic action of spinal sufentanil in patients undergoing orthopedic surgery.

Methods

Fifty-six patients were randomized to one of four groups. Patients were premedicated with 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline or 10 microg sufentanil). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control group received spinal saline and transdermal placebo. The sufentanil group received spinal sufentanil and transdermal placebo. The nitroglycerin group received spinal saline and transdermal nitroglycerine patch. Finally, the sufentanil-nitroglycerin group received spinal sufentanil and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale.

Results

The time to first rescue analgesic medication was longer for the sufentanil-nitroglycerin group (785+/-483 min) compared with the other groups (P<0.005). The time to first rescue analgesics was also longer for the sufentanil group compared with the control group (P<0.05). The sufentanil-nitroglycerin group group required less rescue analgesics in 24 h compared with the other groups (P<0.02) and had lesser 24-h pain visual analog scale scores compared with the control group (P<0.005), although these scores were similar to the sufentanil and nitroglycerin groups (P>0.05). The incidence of perioperative adverse effects was similar among groups (P>0.05).

Conclusions

Transdermal nitroglycerine alone (5 mg/day), a nitric oxide generator, did not result in postoperative analgesia itself, but it prolonged the analgesic effect of spinal sufentanil (10 microg) and provided 13 h of effective postoperative analgesia after knee surgery.
Contraction-Relaxation Coupling and Impaired Left Ventricular Performance in Coronary Surgery Patients
Authors: De Hert Stefan G. , Gillebert Thierry C. , Ten Broecke Pieter W. , Mertens Els , Rodrigus Inez E. , Moulijn Adriaan C.
Published: November 2003

Background

Dependence of left ventricular (LV) relaxation on cardiac systolic load is a function of myocardial contractility. The authors hypothesized that, if a tight coupling would exist between LV contraction and relaxation, the changes in relaxation rate with an increase in cardiac systolic load would be related to the changes in LV contraction.

Methods

Coronary surgery patients (n = 120) with preoperative ejection fraction >40% were included. High-fidelity LV pressure tracings (n = 120) and transgastric transesophageal echocardiographic data (n = 40) were obtained. Hearts were paced at a fixed rate of 90 beats/min. Effects on contraction were evaluated by analysis of changes in dP/dt(max) and stroke area. Effects on relaxation were assessed by analysis of R (slope of the relation between tau and end-systolic pressure). Correlations were calculated with linear regression analysis using Pearson's coefficient r.

Results

Baseline LV end-diastolic pressure was 10+/-3 mm Hg (mean +/- SD). During leg raising, systolic LV pressure increased from 93+/-9 to 107+/-11 mm Hg. The change in dP/dt(max) was variable and ranged from -181 to +254 mm Hg/s. A similar variability was observed with the changes in stroke area, which ranged from -2.0 to +5.5 cm2. Changes in dP/dt(max) and in stroke area were closely related to individual R values (r = 0.87, P<0.001; and r = 0.81, P<0.001, respectively) and to corresponding changes in LV end-diastolic pressure (r = 0.81, P< 0.001; and r = 0.74, P<0.001, respectively).

Conclusions

A tight coupling was observed between contraction and relaxation. Leg raising identified patients who developed a load-dependent impairment of LV performance and increased load dependence of LV relaxation.
A Double-blind Comparison of 0.125% Ropivacaine with Sufentanil and 0.125% Bupivacaine with Sufentanil for Epidural Labor Analgesia
Authors: Gautier Philippe , De Kock Marc , Van Steenberge Albert , Miclot Dominique , Fanard Luc , Hody Jean Luc
Published: November 2003

Background

This study intends to evaluate the benefits of the administration of intermittent bolus doses of ropivacaine (0.125%) compared with bupivacaine (0.125%) after addition of sufentanil for analgesia during labor.

Methods

One hundred thirty American Society of Anesthesiologists physical status 1 or 2 parturients were studied. The 90 initial patients were assigned randomly to receive 10 ml bupivacaine, 0.125%, plus 7.5 microg sufentanil (initial bupivacaine 0.125% group) or ropivacaine, 0.125%, plus 7.5 microg sufentanil (ropivacaine 0.125% group). Forty additional patients were recruited and received 0.125% bupivacaine plus 7.5 microg sufentanil (additional bupivacaine 0.125% group) or 0.100% bupivacaine plus 7.5 microg sufentanil (additional bupivacaine 0.100% group). The duration of analgesia, visual analogue scores for pain, motor blockade (using a six-point modified Bromage scale), patient satisfaction scores, nausea, pruritus, heart rate, and blood pressure were recorded.

Results

Bupivacaine 0.125% and ropivacaine 0.125% coadministered with sufentanil provided rapid and complete analgesia. Onset of analgesia occurred after +/-15 min and lasted +/-90 min. After the third epidural injection, patients in the ropivacaine group experienced significantly less severe motor blockade than patients in the initial bupivacaine 0.125% group. At this point, 93% of the patients in the ropivacaine group were free from motor impairment versus 66% in the bupivacaine group (P<0.05). Comparable levels of motor blockade were obtained in both additional groups. Patients' evaluation of their analgesia was worst in the bupivacaine 0.100% group.

Conclusions

Ropivacaine 0.125% with sufentanil affords reliable analgesia with minimal motor blockade.
Sympathetic Ganglionic Blockade Masks Beneficial Effect of Isoflurane on Histologic Outcome from Near-complete Forebrain Ischemia in the Rat
Authors: Mackensen Burkhard G. , Nellgard Bengt , Miura Yoshihide , Chu Charleen T. , Dexter Franklin , Pearlstein Robert D. , Warner David S.
Published: November 2003

Background

Isoflurane-anesthetized rats have better outcome from global cerebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentrations depend on the anesthetic agent and whether sympathetic ganglionic blockade affects anesthetic-mediated differences in outcome from near-complete forebrain ischemia.

Methods

For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mm Hg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 microg x kg(-1) x h(-1)) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia.

Results

In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P<0.01). Trimethaphan blocked all changes in plasma catecholamine concentrations (P<0.02). In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl-nitrous oxide (43+/-22% vs. 87+/-10%; P<0.001). Trimethaphan abolished the beneficial effects of isoflurane (91+/-6%; P<0.001). Similar observations were made in the cortex.

Conclusions

Isoflurane attenuated the peripheral sympathetic response to ischemia and improved histologic outcome compared with fentanyl and nitrous oxide. This outcome benefit was reversed by sympathetic ganglionic blockade. The beneficial effects of isoflurane may result from a neuroprotective influence of an intermediate sympathetic response that is abolished by trimethaphan.
Hyperbaric Spinal Ropivacaine
Authors: McDonald Susan B. , Liu Spencer S. , Kopacz Dan J. , Stephenson Carol A.
Published: November 2003

Background

Ropivacaine is a newly introduced local anesthetic that may be a useful alternative to low-dose bupivacaine for outpatient spinal anesthesia. However, its relative potency to bupivacaine and its dose-response characteristics are unknown. This double-blind, randomized, crossover study was designed to determine relative potencies of low-dose hyperbaric spinal ropivacaine and bupivacaine and to assess the suitability of spinal ropivacaine for outpatient anesthesia.

Methods

Eighteen healthy volunteers were randomized into three equal groups to receive one spinal administration with bupivacaine and a second with ropivacaine, of equal-milligram doses (4, 8, or 12 mg) of 0.25% drug with 5% dextrose. The duration of blockade was assessed with (1) pinprick, (2) transcutaneous electrical stimulation, (3) tolerance to high tourniquet, (4) electromyography and isometric force dynamometry, and (5) achievement of discharge criteria. Differences between ropivacaine and bupivacaine were assessed with linear and multiple regression. P < 0.05 was considered significant.

Results

Ropivacaine and bupivacaine provided dose-dependent prolongation of sensory and motor block and time until achievement of discharge criteria (R2 ranges from 0.33-0.99; P values from < 0.001 through 0.01). Spinal anesthesia with ropivacaine was significantly different from bupivacaine and was approximately half as potent for all criteria studied. A high incidence of back pain (28%; P = 0.098) was noted after intrathecal ropivacaine was given.

Conclusion

Ropivacaine is half as potent and in equipotent doses has a similar profile to bupivacaine with a higher incidence of side effects. Low-dose hyperbaric spinal ropivacaine does not appear to offer an advantage over bupivacaine for use in outpatient anesthesia.
Preoperative Fasting Practices in Pediatrics
Authors: Ferrari Lynne R. , Rooney Fiona M. , Rockoff Mark A.
Published: November 2003

Background

The purpose of this study was to determine current practice patterns for preoperative fasting at major pediatric hospitals.

Methods

Fasting guidelines for children at each of the hospitals listed in the second edition of the Directory of Pediatric Anesthesiology Fellowship Programs were solicited and analyzed.

Results

Fifty-one institutions were surveyed, and 44 responded. In 50%, clear fluids were permitted up to 2 h prior to anesthesia for all children. Breast milk was restricted to 4 h for children younger than 6 months in 61% of hospitals. Institutions were equally divided (39% each) between a 4-h and a 6-h fast for formula in infants younger than 6 months; for infants older than 6 months, 50% of hospitals restricted formula feeding to 6 h. There was no consensus for solid feeding in children younger than 3 yr, but 50% of hospitals agree that solids should be restricted after midnight in children older than 3 yr.

Conclusions

There is no uniform fasting practice for children before elective surgery in the United States and Canada. However, there is agreement among most institutions that ingestion of clear fluids 2-3 h prior to general anesthesia is acceptable. Most also accept a 4-h restriction for breast milk and a 6-h restriction for nonhuman formula. There is great diversity among institutions regarding fasting for solids in children, with many restricting intake after midnight. There is little agreement about whether infant formula should be treated in the same way as solid food or how to categorize breast milk.
Ropivacaine or 2% Mepivacaine for Lower Limb Peripheral Nerve Blocks
Authors: Casati Andrea , Fanelli Guido , Borghi Battista , Torri Giorgio
Published: November 2003

Background

Intra- and postoperative clinical properties of sciatic-femoral nerve block performed with either ropivacaine at different concentrations or mepivacaine have been evaluated in a multicenter, randomized, blinded study.

Methods

Adult patients scheduled for foot and ankle surgery were randomized to receive combined sciatic-femoral nerve block with 225 mg of either 0.5% (n = 83), 0.75% (n = 87), or 1% (n = 86) ropivacaine, or with 500 mg of 2% mepivacaine (n = 84). A thigh tourniquet was used in all patients. Onset time, adequacy of surgical anesthesia, time to offset of nerve block, and time until first postoperative requirement for pain medication were evaluated by a blinded observer.

Results

The adequacy of nerve block was similar in the four treatment groups (the ratios between adequate:inadequate: failed blocks were 74:9:0 with 0.5% ropivacaine, 74:13:0 with 0.75% ropivacaine, 78:8:0 with 1% ropivacaine, and 72:12:0 with 2% mepivacaine). The onset of the block was slower with 0.5% ropivacaine than with other anesthetic solutions (P < 0.001). Regardless of the concentration, ropivacaine produced a longer motor blockade (10.5+/-3.8 h, 10.3+/-4.3 h, and 10.2+/-5.1 h with 0.5%, 0.75%, and 1% ropivacaine, respectively) than with mepivacaine (4.3+/-2.6 h; P < 0.001). The duration of postoperative analgesia was shorter after mepivacaine (5.1+/-2.7 h) than after ropivacaine (12.2+/-4.1 h, 14.3+/-5 h, and 14.5+/-3.4 h, with 0.5%, 0.75%, or 1% ropivacaine, respectively; P < 0.001). Pain relief after 0.5% ropivacaine was 14% shorter than 0.75% or 1% ropivacaine (P < 0.05). During the first 24 h after surgery, 30-37% of patients receiving ropivacaine required no analgesics compared with 10% of those receiving mepivacaine (P < 0.001).

Conclusions

This study suggests that 0.75% ropivacaine is the most suitable choice of local anesthetic for combined sciatic-femoral nerve block, providing an onset similar to mepivacaine and prolonged postoperative analgesia.
Nerve Injury Associated with Anesthesia
Authors: Cheney Frederick W. , Domino Karen B. , Caplan Robert A. , Posner Karen L.
Published: November 2003

Background

Nerve injury associated with anesthesia is a significant source of morbidity for patients and liability for anesthesiologists. To identify recurrent and emerging patterns of injury we analyzed the current American Society of Anesthesiologists (ASA) Closed Claims Project Database and performed an in-depth analysis of claims for nerve injury that were entered into the database since the authors' initial report of the subject.

Methods

The ASA Closed Claims Database is a standardized collection of case summaries derived from the closed claims files of professional liability insurance companies. Claims for nerve injury that were not included in the authors' 1990 report were reviewed in-depth.

Results

Six hundred seventy (16% of 4,183) claims were for anesthesia-related nerve injury. The most frequent sites of injury were the ulnar nerve (28%), brachial plexus (20%), lumbosacral nerve root (16%), and spinal cord (13%). Ulnar nerve (85%) injuries were more likely to have occurred in association with general anesthesia, whereas spinal cord (58%) and lumbosacral nerve root (92%) injuries were more likely to occur with regional techniques. Ulnar nerve injury occurred predominately in men (75%) and was also more apt to have a delayed onset of symptoms (62%) than other nerve injuries. Spinal cord injuries were the leading cause of claims for nerve injury that occurred in the 1990s.

Conclusion

New strategies for prevention of nerve damage cannot be recommended at this time because the mechanism for most injuries, particularly those of the ulnar nerve, is not apparent.
Rapid Saline Infusion Produces Hyperchloremic Acidosis in Patients Undergoing Gynecologic Surgery
Authors: Scheingraber Stefan , Rehm Markus , Sehmisch Christiane , Finsterer Udilo
Published: November 2003

Background

Changes in acid-base balance caused by infusion of a 0.9% saline solution during anesthesia and surgery are poorly characterized. Therefore, the authors evaluated these phenomena in a dose-response study.

Methods

Two groups of 12 patients each who were undergoing major intraabdominal gynecologic surgery were assigned randomly to receive 0.9% saline or lactated Ringer's solution in a dosage of 30 ml x kg(-1) x h(-1). The pH, arterial carbon dioxide tension, and serum concentrations of sodium, potassium, chloride, lactate, and total protein were measured in 30-min intervals. The serum bicarbonate concentration was calculated using the Henderson-Hasselbalch equation and also using the Stewart approach from the strong ion difference and the amount of weak plasma acid. The strong ion difference was calculated as serum sodium + serum potassium - serum chloride - serum lactate. The amount of weak plasma acid was calculated as the serum total protein concentration in g/dl x 2.43.

Results

Infusion of 0.9% saline, but not lactated Ringer's solution, caused a metabolic acidosis with hyperchloremia and a concomitant decrease in the strong ion difference. Calculating the serum bicarbonate concentration using the Henderson-Hasselbalch equation or the Stewart approach produced equivalent results.

Conclusions

Infusion of approximately 30 ml x kg(-1) x h(-1) saline during anesthesia and surgery inevitably leads to metabolic acidosis, which is not observed after administration of lactated Ringer's solution. The acidosis is associated with hyperchloremia.
Perianesthetic Dental Injuries
Authors: Warner Mary E. , Benenfeld Steven M. , Warner Mark A. , Schroeder Darrell R. , Maxson Pamela M.
Published: November 2003

Background

Dental injury is well-recognized as a potential complication of laryngoscopy and tracheal intubation. However, the frequency, outcomes, and risk factors for this problem have not been documented in a well-defined patient population.

Methods

The authors analyzed the dental injuries of 598,904 consecutive cases performed on patients who required anesthetic services from 1987 through 1997. Dental injuries were defined as perianesthetic events (those occurring within 7 days) that required dental interventions to repair, stabilize, or extract involved dentition or support structures. A 1:3 case-control study of 16 patient and procedural characteristics was performed for cases that occurred during the first 5 yr of the study. Conditional logistic regression was used for data analysis.

Results

There were 132 cases (1:4,537 patients) of dental injury. One half of these injuries occurred during laryngoscopy and tracheal intubation. The upper incisors were the most commonly involved teeth, and most injuries were crown fractures and partial dislocations and dislodgements. Multivariate risk factors for dental injury in the case control study included general anesthesia with tracheal intubation (odds ratio [OR] = 89), preexisting poor dentition (OR = 50), and increased difficulty of laryngoscopy and intubation (OR = 11).

Conclusions

Based on these data from a large surgical population at a single training institution, approximately 1:4,500 patients who receive anesthesia services sustain a dental injury that requires repair or extraction. Patients most at risk for perianesthetic dental injury include those with preexisting poor dentition who have one or more risk factors for difficult laryngoscopy and tracheal intubation.
Use of the Cuffed Oropharyngeal Airway as an Alternative to the Laryngeal Mask Airway with Positive-pressure Ventilation
Authors: van Vlymen Janet M. , Fu Wen , White Paul F. , Klein Kevin W. , Griffin James D.
Published: November 2003

Background

The cuffed oropharyngeal airway is a modified Guedel-type oral airway with a cuff at its distal end. The objectives of this study were to compare the ability of the cuffed oropharyngeal airway and the laryngeal mask airway to provide positive-pressure ventilation during general anesthesia, and to assess their relative ease of use and ability to reduce total fresh gas flow rates.

Methods

In this prospective, randomized study, a cuffed oropharyngeal airway (n = 25) or a laryngeal mask airway (n = 25) device was inserted after induction of anesthesia intravenously using 2 mg/kg propofol. While anesthesia was maintained with sevoflurane and nitrous oxide, the leak pressure, leak fraction (the fractional difference between the inspired and expired tidal volume), minimum fresh gas flow rate, and need for airway manipulations were determined. The anesthesia provider who inserted the device completed an evaluation form at the end of the 15-min study period.

Results

Positive-pressure ventilation was established successfully on the first attempt in 92% of the patients when the cuffed oropharyngeal airway was used and in 88% of the patients when the laryngeal mask airway device was used. However, manipulations of the airway device were necessary more frequently (8 vs. 1 patient; P < 0.05) and the leak pressure was less (22 +/- 6 cm water vs. 26 +/- 5 cm water; P < 0.05) with the cuffed oropharyngeal airway than with the laryngeal mask airway. In addition, the leak fraction (0.19 +/- 0.18 vs. 0.31 +/- 0.22; P < 0.05) and the minimum fresh gas flow rate (1.3 +/- 1.5 vs. 2.4 +/- 2.5; P = 0.12) were less in the laryngeal mask airway group.

Conclusions

Positive-pressure ventilation is possible with the laryngeal mask airway and cuffed oropharyngeal airway devices. Although the cuffed oropharyngeal airway can be inserted easily by inexperienced users with a high first-attempt success rate (> 90%), manipulations of the device may be required to maintain a patent airway. The laryngeal mask airway device allows positive-pressure ventilation at slightly greater peak inspiratory pressures.
Sex Differences in Morphine-induced Ventilatory Depression Reside within the Peripheral Chemoreflex Loop
Authors: Sarton Elise , Teppema Luc , Dahan Albert
Published: November 2003

Background

This study gathers information in humans on the sites of sex-related differences in ventilatory depression caused by the mu-opioid receptor agonist morphine.

Methods

Experiments were performed in healthy young men (n = 9) and women (n = 7). Dynamic ventilatory responses to square-wave changes in end-tidal carbon dioxide tension (7.5-15 mmHg) and step decreases in end-tidal oxygen tension (step from 110 to 50 mmHg, duration of hypoxia 15 min) were obtained before and during morphine infusion (intravenous bolus dose 100 microg/kg, followed by 30 microg x kg(-1) x h(-1)). Each hypercapnic response was separated into a fast peripheral and slow central component, which yield central (Gc) and peripheral (Gp) carbon dioxide sensitivities. Values are mean +/- SD.

Results

In carbon dioxide studies in men, morphine reduced Gc from 1.61 +/- 0.33 to 1.23 +/- 0.12 l x min(-1) x mmHg(-1) (P < 0.05) without affecting Gp (control, 0.41 +/- 0.16 and morphine, 0.49 +/- 0.12 l x min(-1) x mmHg(-1), not significant). In carbon dioxide studies in women, morphine reduced Gc, from 1.51 +/- 0.74 to 1.17 +/- 0.52 l x min(-1) x mmHg(-1) (P < 0.05), and Gp, from 0.54 +/- 0.19 to 0.39 +/- 0.22 l x min(-1) x mmHg(-1) (P < 0.05). Morphine-induced changes in Gc were equal in men and women; changes in Gp were greater in women. In hypoxic studies, morphine depressed the hyperventilatory response at the initiation of hypoxia more in women than in men (0.54 +/- 0.23 vs. 0.26 +/- 0.34 l x min(-1) x %(-1), respectively; P < 0.05). The ventilatory response to sustained hypoxia (i/e., 15 min) did not differ between men and women.

Conclusions

The data indicate the existence of sex differences in morphine-induced depression of responses mediated via the peripheral chemoreflex pathway, with more depression in women, but not of responses mediated via the central chemoreflex pathway. In men and women, morphine did not change the translation of the initial hyperventilatory response to short-term hypoxia into the secondary decrease in inspired minute ventilation (Vi) caused by sustained hypoxia.
Effect of Sevoflurane and Desflurane on the Myogenic Constriction and Flow-induced Dilation in Rat Coronary Arterioles
Authors: Park Kyung W. , Dai Hai B. , Lowenstein Edward , Sellke Frank W.
Published: November 2003

Background

Determinants of myocardial blood flow distribution include metabolic, myogenic, endothelial, and neurohumoral control mechanisms. The authors studied the effect of sevoflurane and desflurane on the myogenic and endothelial mechanisms.

Methods

Wistar rat subepicardial microvessels, approximately 100 microm in diameter, were monitored for diameter changes in vitro using a video detection system. Myogenic vasomotion was studied by varying the intraluminal pressure from 10 mmHg to 120 mmHg. Flow-induced, endothelium-dependent dilation was evaluated in U46619-preconstricted vessels by varying the pressure gradient across the isolated vessel from 10 mmHg to 80 mmHg, while maintaining the midpoint luminal pressure constant at 40 mmHg to avoid myogenic effects. Myogenic and flow-induced vasomotion both were studied in the presence of sevoflurane, 1 or 2 minimum alveolar concentration (MAC) (MAC is a unit of inhalational anesthetic potency), desflurane, 1 or 2 MAC, or no anesthetic (control).

Results

Myogenic constriction was shown above intraluminal pressures of 70 mmHg. Myogenic constriction was unchanged by sevoflurane, 1 MAC (P = 0.24), but was mildly enhanced by sevoflurane, 2 MAC (P < 0.05), or desflurane, 1 (P < 0.05) or 2 MAC (P < 0.01). Flow-induced dilation was shown over the pressure gradient range of 10-80 mmHg. Flow-induced dilation was not altered significantly by sevoflurane, 1 or 2 MAC (P > 0.3 each), but was significantly attenuated by desflurane, 1 or 2 MAC (P < 0.001 each).

Conclusions

Sevoflurane maintains myogenic and endothelial determinants of myocardial blood flow distribution. Conversely, desflurane attenuates endothelium-dependent flow-induced dilation while mildly enhancing myogenic constriction.
Extreme, Progressive Isovolemic Hemodilution with 5% Human Albumin, PentaLyte, or Hextend Does Not Cause Hepatic Ischemia or Histologic Injury in Rabbits
Authors: Nielsen Vance G. , Baird Manuel S. , Brix Amy E. , Matalon Sadis
Published: November 2003

Background

Physicians and their patients are greatly concerned about perioperative blood administration. Although isovolemic hemodilution is utilized to decrease the incidence of transfusion, it is unclear at what degree of hemodilution hepatoenteric ischemia and injury occurs. The authors hypothesized that hepatic ischemia, systemic ischemia, and tissue injury would occur during hemodilution in rabbits, and that the severity of ischemia and injury may be dependent on the fluid administered.

Methods

Rabbits anesthetized with isoflurane were assigned randomly to a sham-operated group (n = 8) or groups that underwent four isovolemic hemodilutions (25% of the blood volume removed at hourly intervals), with blood replaced with one of three solutions: balanced electrolyte solutions containing 6% pentastarch (n = 8), 6% hetastarch (n = 9), or 5% human albumin in normal saline (n = 8). Arterial ketone body ratio and plasma lactate, respectively, served as measures of hepatic and systemic ischemia. Gastric, duodenal, and hepatic histologic injury was assessed post mortem.

Results

Hemodilution from a baseline hematocrit of about 33% to about 8% (third hemodilution) with all three colloids did not result in a significant increase in plasma lactate concentration or decrease in arterial ketone body ratio. At a hematocrit of about 5% (fourth hemodilution), the hetastarch group had a significantly (P < 0.05) greater plasma lactate concentration than the sham-operated and 5% human albumin groups. There were no significant differences in arterial ketone body ratio or histologic injury between the groups.

Conclusions

Isovolemic hemodilution (approximately 5% hematocrit) with albumin, pentastarch, or hetastarch solutions does not result in significant hepatic ischemia or injury assessed by histology.
Effects of Sevoflurane on Regional Myocardial Blood Flow Distribution
Authors: Kitahata Hiroshi , Kawahito Shinji , Nozaki Junpei , Kimura Hideyuki , Tanaka Katsuya , Kitagawa Tetsuya , Oshita Shuzo
Published: November 2003

Background

Using myocardial contrast echocardiography, the authors tried to determine whether sevoflurane causes myocardial blood maldistribution in humans and dogs.

Methods

In animal experiments, 15 mongrel dogs were organized into dipyridamole (n = 6) and sevoflurane (n = 9) groups. Sonicated albumin was infused into the left main coronary artery. The peak gray level corrected for background was analyzed at the following intervals: (1) at baseline, (2) after stenosis of the left circumflex coronary artery (blood flow reduced by 40%), (3) after administration of dipyridamole (1 mg/kg given intravenously) or sevoflurane (1 minimum alveolar concentration) during stenosis, and (4) after phenylephrine during stenosis and administration of dipyridamole or sevoflurane. In human studies, nine patients undergoing coronary artery bypass grafting were studied. During partial extracorporeal circulation, the peak gray level was analyzed before and 20 min after sevoflurane (1 minimum alveolar concentration).

Results

In animal experiments, dipyridamole decreased significantly the inner:outer ratio of the peak gray level in the ischemic area and the ischemic:normal ratio of the peak gray level. After arterial pressure was restored with phenylephrine, neither the inner:outer ratio nor the ischemic:normal ratio improved. In contrast, after sevoflurane administration, the inner:outer ratio and the ischemic:normal ratio remained unchanged, but these increased with phenylephrine. In human studies, sevoflurane did not change the inner:outer ratio in the area supplied by the most stenotic coronary artery.

Conclusion

These results suggest that dipyridamole, a potent coronary vasodilator, produces maldistribution of coronary blood flow in our dog models, whereas sevoflurane does not do this in animal or human studies.
Propofol Prevents Peroxide-induced Inhibition of Glutamate Transport in Cultured Astrocytes
Authors: Sitar Sandra M. , Hanifi-Moghaddam Pejman , Gelb Adrian , Cechetto David F. , Siushansian Ramin , Wilson John X.
Published: November 2003

Background

Glutamate transporters located in the plasma membrane of cerebral astrocytes take up excitatory neurotransmitters from the synaptic cleft. In diseases characterized by oxidative stress, the extracellular glutamate concentration increases and contributes to neuronal death. The authors wanted to determine whether propofol defends brain cells against oxidant-induced changes in their transport of glutamate.

Methods

Primary cultures of rat cerebral astrocytes were exposed to tert-butyl hydroperoxide (1 mM) to serve as an in vitro model of oxidative stress. Astrocytes were incubated with propofol for 2 h and tert-butyl hydroperoxide was added for the final hour. Alternatively, astrocytes were incubated with tert-butyl hydroperoxide for 30 min and then with propofol for another 30 min. Control cells received drug vehicle rather than propofol. The rate of uptake of glutamate, the efflux of the nonmetabolizable analog D-aspartate, and the intracellular concentration of the endogenous antioxidant glutathione were measured.

Results

Tert-butyl hydroperoxide decreased the glutathione concentration and inhibited glutamate uptake but had a negligible effect on D-aspartate efflux. At clinically relevant concentrations, propofol did not affect the glutathione concentration but did prevent the effect of tert-butyl hydroperoxide on glutamate transport. Furthermore, the addition of propofol after tert-butyl hydroperoxide reversed the inhibition of glutamate uptake.

Conclusions

Propofol prevents and reverses the inhibition of excitatory amino acid uptake in astrocytes exposed to tert-butyl hydroperoxide. The ability of propofol to defend against peroxide-induced inhibition of glutamate clearance may prevent the pathologic increase in extracellular glutamate at synapses, and thus delay or prevent the onset of excitotoxic neuronal death.
Oral Ketamine and Transdermal Nitroglycerin as Analgesic Adjuvants to Oral Morphine Therapy for Cancer Pain Management
Authors: Lauretti Gabriela R. , Lima Izabel C. P. R. , Reis Marlene P. , Prado Wiliam A. , Pereira Newton L.
Published: November 2003

Background

Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner. This study was designed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine in cancer pain therapy.

Methods

After institutional approval and informed patient consent were obtained, 60 patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and any adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing "the worst possible pain" was introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime. The morphine regimen was adjusted individually to a maximal oral dose of 80-90 mg/day to keep the visual analog scale score less than 4. When patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4.

Results

The groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced were similar among the groups. The daily consumption of oral morphine was as follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20: CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG (P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and DG groups reported somnolence, but patients in the NG and KG groups did not.

Conclusions

Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management.
Determination of the Potency of Remifentanil Compared with Alfentanil Using Ventilatory Depression as the Measure of Opioid Effect
Authors: Glass Peter S. A. , Iselin-Chaves Irene A. , Goodman David , Delong Elizabeth , Hermann David J.
Published: November 2003

Background

Remifentanil is a new opioid with properties similar to other mu-specific agonists. To establish its pharmacologic profile relative to other known opioids, it is important to determine its potency. This study investigated the relative potency of remifentanil compared with alfentanil.

Methods

Thirty young healthy males were administered double-blind remifentanil or alfentanil intravenously for 180 min using a computer-assisted continuous infusion device. Depression of ventilation was assessed by the minute ventilatory response to 7.5% CO2 administered via a "bag in the box" system. The target concentration of the study drug was adjusted to obtain 40-70% depression of baseline minute ventilation. Multiple blood samples were obtained during and following the infusion. The concentration-effect relationship of each drug was modeled, and the concentration needed to provide a 50% depression of ventilation (EC50) was determined.

Results

Only 11 subjects in each drug group completed the study; however, there were sufficient data in 28 volunteers to model their EC50 values. The EC50 (mean and 95% confidence interval) for depression of minute ventilation with remifentanil was 1.17 (0.85-1.49) ng/ml and the EC50 for alfentanil was 49.4 (32.4-66.5) ng/ml.

Conclusion

Based on depression of the minute ventilatory response to 7.5% CO2, remifentanil is approximately 40 (26-65) times more potent than alfentanil when remifentanil and alfentanil whole-blood concentrations are compared. As alfentanil is usually measured as a plasma concentration, remifentanil is approximately 70 (41-104) times more potent than alfentanil when remifentanil whole-blood concentration is compared with alfentanil plasma concentration. This information should be used when performing comparative studies between remifentanil and other opioids.
Propofol Requirement Is Decreased in Patients with Large Supratentorial Brain Tumor
Authors: Chan Matthew T. V. , Gin Tony , Poon Wai S.
Published: November 2003

Background

The anesthetic requirement is decreased in animals with head injury, but there are no data regarding the effect of intracranial tumor on the potency for intravenous anesthetics. The authors compared the quantal dose-response curves for propofol in patients having large (> or = 30 mm, mass effect) brain tumor with those having smaller (< 30 mm) lesions and with control patients undergoing noncranial surgery.

Methods

Sixty patients in each group were randomly assigned to receive one of the six doses of propofol (0.5, 0.7, 1.0, 1.3, 1.8, or 2.5 mg/kg) over 10 s. Two minutes after drug administration, patients were asked to open their eyes as a test for response to verbal command. Patients who failed to respond were given a 10-s, 50-Hz, 80-mA transcutaneous tetanic electrical current to the ulnar nerve as a test for response to painful stimulus. Purposeful movement indicated positive response. Log dose-response curves for loss of response to verbal command and tetanic stimulus were calculated after logit transformation.

Results

The median effective doses (ED50s; 95% confidence interval) for suppressing response to verbal command and tetanic stimulus were 0.75 (0.65-0.86) mg/kg and 1.28 (1.11-1.49) mg/kg, respectively, in patients with large brain tumor. These values were significantly less than the corresponding ED50s in patients with small tumor, 1.01 (0.88-1.15) mg/kg and 1.76 (1.51-2.07) mg/kg, or healthy control subjects, 0.98 (0.86-1.12) mg/kg and 1.89 (1.62-2.23) mg/kg.

Conclusions

The doses of propofol required to suppress response to verbal command and tetanic stimulus were 23% less and 32% less in patients with large brain tumor compared with control subjects. Small tumor did not affect potency of propofol.
The Independent Effect of Propofol Anesthesia on Whole Body Protein Metabolism in Humans
Authors: Schricker Thomas , Klubien Kristine , Carli Franco
Published: November 2003

Background

The purpose of this study was to examine the effect of general anesthesia with propofol in the absence of surgical stimulation on whole body protein metabolism.

Methods

Six unpremedicated patients were studied. General anesthesia included propofol (120 microg x kg(-1) x min(-1)), vecuronium bromide, and oxygen-enriched air. Changes in protein breakdown, protein oxidation, and synthesis were measured by an isotope dilution technique using a constant infusion of the stable isotope tracer L-[1-13C]leucine (0.008 mg x kg(-1) x min(-1)) before and during 100 min of propofol anesthesia. The plasma concentrations of glucose, lactate, non-esterified fatty acids, and cortisol were measured before and during anesthesia.

Results

An isotopic steady state of plasma [1-13C]alpha-ketoisocaproate (taken to represent the intracellular leucine precursor pool enrichment for protein synthesis) and expired 13C-carbon dioxide were obtained before and during propofol infusion. Whole body protein breakdown decreased during propofol anesthesia by 6% (P < 0.05), whereas protein synthesis and oxidation did not change significantly. Plasma concentration of cortisol decreased after 90 min of propofol anesthesia (P < 0.05). No significant changes of plasma concentrations of glucose, lactate, and non-esterified fatty acids occurred during propofol administration.

Conclusions

Propofol anesthesia did not significantly affect whole body protein synthesis and oxidation but caused a small, although significant, decrease in whole body protein breakdown, possibly mediated through the suppression of plasma cortisol concentration.
A Prospective Randomized Comparison of Three Blood Conservation Strategies for Radical Prostatectomy
Authors: Monk Terri G. , Goodnough Lawrence T. , Brecher Mark E. , Colberg John W. , Andriole Gerald L. , Catalona William J.
Published: November 2003

Background

Preoperative autologous blood donation is a standard of care for elective surgical procedures requiring transfusion. The authors evaluated the efficacy of alternative blood-conservation strategies including preoperative recombinant human erythropoietin (rHuEPO) therapy and acute normovolemic hemodilution (ANH) in radical retropubic prostatectomy patients.

Methods

Seventy-nine patients were prospectively randomized to preoperative autologous donation (3 U autologous blood); rHuEPO plus ANH (preoperative subcutaneous administration of 600 U/kg rHuEPO at 21 and 14 days before surgery and 300 U/kg on day of surgery followed by ANH in the operating room); or ANH (blinded, placebo injections per the rHuEPO regimen listed previously). Transfusion outcomes, perioperative hematocrit levels, postoperative outcomes, and blood-conservation costs were compared among the three groups.

Results

Baseline hematocrit levels were similar in all groups (43%+/-2%). On the day of surgery hematocrit decreased to 34% +/-4% in the preoperative autologous donation group (P < 0.001), increased to 47%+/-2% in the rHuEPO plus ANH group (P < 0.001), and remained unchanged at 43%+/-2% in the ANH group. Allogeneic blood exposure was similar in all groups. The rHuEPO plus ANH group had significantly higher hematocrit levels compared with the other groups throughout the hospitalization (P < 0.001). Average transfusion costs were significantly lower for ANH ($194+/-$192) compared with preoperative autologous donation ($690+/-$128; P < 0.001) or rHuEPO plus ANH ($1,393+/-$204, P < 0.001).

Conclusions

All three blood-conservation strategies resulted in similar allogeneic blood exposure rates, but ANH was the least costly technique. Preoperative rHuEPO plus ANH prevented postoperative anemia but resulted in the highest transfusion costs.
Management of Bladder Function after Outpatient Surgery
Authors: Pavlin Janet D. , Pavlin Edward G. , Fitzgibbon Dermot R. , Koerschgen Meagan E. , Plitt Terryn M.
Published: November 2003

Background

This study was designed to test a treatment algorithm for management of bladder function after outpatient general or local anesthesia.

Methods

Three hundred twenty-four outpatients, stratified into risk categories for urinary retention, were studied. Patients in category 1 were low-risk patients (n = 227) having non-pelvic surgery and randomly assigned to receive 10 ml/kg or 2 ml/kg of intravenous fluid intraoperatively. They were discharged when otherwise ready, without being required to void. Patients in category 2 (n = 40), also presumed to be low risk, had gynecologic surgery. High-risk patients included 31 patients having hernia or anal surgery (category 3), and 31 patients with a history of retention (category 4). Bladder volumes were monitored by ultrasound in those in categories 2-4, and patients were required to void (or be catheterized) before discharge. The incidence of retention and urinary tract symptoms after surgery were determined for all categories.

Result

Urinary retention affected 0.5% of category 1 patients and none of category 2 patients. Median time to void after discharge was 75 min (interquartile range 120) in category 1 patients (n = 27) discharged without voiding. Fluids administered did not alter incidence of retention or time to void. Retention occurred in 5% of high-risk patients before discharge and recurred in 25% after discharge.

Conclusion

In reliable patients at low risk for retention, voiding before discharge appears unnecessary. In high-risk patients, continued observation until the bladder is emptied is indicated to avoid prolonged overdistention of the bladder.
Contractility in Humans after Coronary Artery Surgery
Authors: Schmidt Christoph , Roosens Carl , Struys Michel , Deryck Yvon L. J. M. , Van Nooten Guido , Colardyn Francis , Van Aken Hugo , Poelaert Jan I.
Published: November 2003

Background

Propofol's unique pharmacokinetic profile offers advantages for titration and rapid emergence in patients after coronary artery bypass graft (CABG) surgery, but concern for negative inotropic properties potentially limits its use in these patients. The current study analyzed the effect of various propofol plasma concentrations on left ventricular (LV) contractility by means of a single-beat contractile index based on LV maximal power (PWR(max)).

Methods

The study was conducted in 30 patients after CABG surgery. Immediately after admission to the intensive care unit (ICU), four different plasma concentrations of propofol 0.65, 1.30, 1.95, and 2.60 microg/ml were established. At each concentration level, the cardiac and vascular effects of propofol were studied by combining echocardiographic data with invasively derived aortic root pressure. Preload was characterized by LV end-diastolic dimensions. Afterload was indicated in terms of indexed systemic vascular resistance (SVRI), LV end-systolic meridional wall stress (LV-ESWS), and arterial elastance (Ea). Quantification of effects on contractility was achieved by preload-adjusted PWRmax.

Results

Myocardial contractility did not change during a fourfold increase in propofol plasma concentration. Preload-adjusted PWRmax amounted to 3.90+/-1.75 W x ml(-2) x 10(4), 3.98+/-1.69, 3.94+/-1.70, and 3.88+/-1.72, respectively (mean+/-SD). With respect to ventricular loading conditions, propofol caused a significant reduction in both pre- and afterload.

Conclusions

The current results strongly suggest that propofol lacks direct cardiac depressant effects. Nevertheless, meaningful vascular actions of propofol could be demonstrated. Significant decreases in ventricular loading conditions accounted for a marked decrease in arterial blood pressure and supported the concept that propofol in clinically relevant concentration is a vasodilator.