Anesthesia and analgesia
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Anesthesia and analgesia · Apr 1998
Comparative StudyCardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep.
Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)-bupivacaine. S(-)-bupivacaine (i.e., levobupivacaine) is currently undergoing preclinical evaluation. Cross-over studies with i.v. levobupivacaine and bupivacaine were conducted in two groups of seven conscious sheep. Doses were chosen to avoid convulsions (smaller dose 6.25-37.5 mg/min) or to be potentially toxic (larger dose 75-200 mg/3 min). In subconvulsive doses, both drugs produced similar time- and dose-dependent depression of left ventricular systolic contractility (dP/dt(max)). Convulsions occurred consistently with > or = 75 mg of bupivacaine and > or = 100 mg of levobupivacaine, producing an abrupt reversal of dP/dt(max) depression. Subconvulsive doses produced minor cardiovascular effects on heart rate and blood pressure, whereas both were increased by convulsions. Cardiac output and myocardial blood flow were decreased with larger doses of both drugs. Doses > 75 mg of bupivacaine or > 100 mg of levobupivacaine induced QRS widening and ventricular arrhythmias, but significantly fewer and less deleterious arrhythmias were induced by levobupivacaine. Three animals died after 150, 150, and 200 mg of bupivacaine from the sudden onset of ventricular fibrillation. These doses of levobupivacaine produced nonfatal arrhythmias that automatically returned to sinus rhythm. We conclude that levobupivacaine could offer a greater margin of clinical safety than bupivacaine. ⋯ Levobupivacaine comprises 50% of commercially available bupivacaine and is being considered for use in its own right. Local anesthetics can cause toxicity to the cardiovascular and central nervous systems. As a part of a preclinical evaluation of levobupivacaine, this study compared the toxic effects of levobupivacaine and bupivacaine in sheep.
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Anesthesia and analgesia · Apr 1998
Comparative StudyComparison of ketamine and dextromethorphan in potentiating the antinociceptive effect of morphine in rats.
We compared the efficacy of two clinically available drugs with N-methyl-D-aspartate receptor antagonist properties, dextromethorphan and ketamine, in potentiating morphine-induced antinociception. Ketamine alone at 0.3-3 mg/kg had no effect on the hot plate test and at 10 mg/kg caused sedation/motor deficits. The antinociceptive effect of 5 mg/kg morphine was slightly enhanced by 1 mg/kg, but not 0.3 or 3 mg/kg, ketamine. Dextromethorphan alone at 45 mg/kg had no effect, but at 60 mg/kg caused sedation/motor deficit. At 15-45 mg/kg, dextromethorphan significantly and dose-dependently increased the magnitude and duration of morphine-induced antinociception. Dextromethorphan also potentiated morphine at doses that, by themselves, did not cause antinociception (1-2 mg/kg). ⋯ Dextromethorphan was more effective than ketamine in potentiating morphine-induced antinociception. Dextromethorphan may thus be the drug of choice for testing the interactions between N-methyl-D-aspartate antagonists and morphine clinically.
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Anesthesia and analgesia · Apr 1998
Comparative StudyAntinociceptive potentiation and attenuation of tolerance by intrathecal co-infusion of magnesium sulfate and morphine in rats.
N-methyl-D-aspartate (NMDA) antagonists, such as MK801, delay the development of morphine tolerance. Magnesium, a noncompetitive NMDA antagonist, reduces postoperative morphine requirements. The present study was designed to evaluate the effects of intrathecal co-administration of magnesium sulfate with morphine on antinociceptive potentiation, tolerance, and naloxone-induced withdrawal signs. Magnesium sulfate (40-60 microg/h) co-administration for 7 days, similar to MK801 (10 nmol/h), prevented the decline in antinociceptive response compared with morphine (20 nmol/h). Magnesium sulfate (60 microg/h) produced no antinociception, but co-infused with morphine (1 nmol/h), it resulted in potentiated antinociception compared with morphine throughout the 7-day period. Probe morphine doses after 7-day infusions demonstrated a significantly greater 50% effective dose value for morphine 1 nmol/h (109.7 nmol) compared with saline (10.9 nmol), magnesium sulfate 60 microg/h (10.9 nmol), and magnesium sulfate 60 microg/h plus morphine 1 nmol/h (11.2 nmol), which indicates that magnesium had delayed morphine tolerance. Morphine withdrawal signs after naloxone administration were not altered by the co-infusion of magnesium sulfate. Cerebrospinal fluid magnesium levels after intrathecal magnesium sulfate (60 microg/h) for 2 days increased from 17.0 +/- 1.0 microg/mL to 41.4 +/- 23.6 microg/mL, although serum levels were unchanged. This study demonstrates antinociceptive potentiation and delay in the development of morphine tolerance by the intrathecal coinfusion of magnesium sulfate and morphine in the rat. ⋯ The addition of magnesium sulfate, an N-methyl-D-aspartate antagonist, to morphine in an intrathecal infusion provided better analgesia than morphine alone in normal rats. These results suggest that intrathecal administration of magnesium sulfate may be a useful adjunct to spinal morphine analgesia.
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Anesthesia and analgesia · Apr 1998
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialA comparison of the efficacy, safety, and patient satisfaction of ondansetron versus droperidol as antiemetics for elective outpatient surgical procedures. S3A-409 and S3A-410 Study Groups.
Two identical, randomized, double-blind, placebo-controlled studies enrolled 2061 adult surgical outpatients at high risk of postoperative nausea and vomiting (PONV) to compare i.v. ondansetron 4 mg with droperidol 0.625 mg and droperidol 1.25 mg for the prevention of PONV. The antiemetic drugs or placebo were administered i.v. 20 min before the induction of anesthesia with a barbiturate compound, followed by maintenance with N2O/isoflurane/enflurane. Nausea, emetic episodes, adverse events, and patient satisfaction were analyzed for the 0 to 2 h and 0 to 24 h postoperative periods. In the 0 to 2 h postoperative period, there was a complete response (no emesis or rescue antiemetic) in 46% of subjects given placebo (P < 0.05 versus antiemetic groups), in 62% given ondansetron, in 63% given droperidol 0.625 mg, and in 69% given droperidol 1.25 mg (P < 0.05 versus ondansetron). In the 0 to 24-h postoperative period, there were no significant differences in complete response between the ondansetron and droperidol 0.625 or 1.25 mg groups; all groups remained superior to placebo. The proportion of patients without nausea during the 0 to 24 h postoperative period was greater in the antiemetic groups compared with the placebo group; however, droperidol 1.25 mg was more effective than ondansetron 4 mg or droperidol 0.625 mg (43% vs 29% or 29%, respectively). Headache incidence was higher in the ondansetron group compared with either droperidol group. Patient satisfaction scores did not differ significantly among antiemetic treatment groups, although all were superior to placebo. In conclusion, all antiemetic treatment regimens were superior to placebo for the prevention of PONV in the immediate postoperative period; however, droperidol 1.25 mg was more efficacious than ondansetron during the early recovery period (0-2 h). There were no significant differences between ondansetron and either droperidol dose for emesis prevention during the 0 to 24 h postoperative period. ⋯ More than 2000 patients at high risk of postoperative nausea and vomiting were given either placebo, ondansetron 4 mg, or droperidol 0.625 mg or 1.25 mg i.v. before the administration of general anesthesia. After surgery, the incidence of nausea, vomiting, medication side effects, and patient satisfaction were evaluated for 24 h. Droperidol 0.625 or 1.25 mg i.v. compared favorably with ondansetron 4 mg i.v. for the prevention of postoperative nausea and vomiting after ambulatory surgery.
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Anesthesia and analgesia · Apr 1998
Randomized Controlled Trial Comparative Study Clinical TrialIs there a better right-sided tube for one-lung ventilation? A comparison of the right-sided double-lumen tube with the single-lumen tube with right-sided enclosed bronchial blocker.
Anatomic variation between tracheal carina and the take-off of the right upper bronchus often makes the use of a right-sided double-lumen tube (R-DLT) or a single-lumen tube with right-sided enclosed bronchial blocker tube (R-UBB) (Univent) undesirable. This study compared the R-DLT with the R-UBB to determine whether there was any advantage of one over the other during anesthesia with one-lung ventilation (OLV) for right-sided thoracic surgeries. Forty patients requiring right lung deflation were randomly assigned to one of two groups. Twenty patients received a right-sided BronchoCath double-lumen tube, and 20 received a Univent tube with a bronchial blocker placed in the right mainstem bronchus. The following were studied: 1) time required to position each tube until satisfactory placement was achieved; 2) number of times that fiberoptic bronchoscopy was required (including one with the patient supine and one in lateral decubitus position); 3) number of malpositions after initial confirmation of tube placement; 4) time required until lung collapse; 5) surgical exposure; and 6) cost of tubes per case. No differences were found with any of these variables except that the cost of acquisition overall was greater for the R-UBB than for the R-DLT. No right upper lobe collapse was observed in the postoperative period in the chest radiograph in any of the patients studied. We conclude that either tube can be used safely and effectively for right-sided thoracic surgeries that require anesthesia for OLV. ⋯ In this study, right-sided double-lumen tubes were compared with the Univent with right-sided bronchial blockers. The results indicate that either tube can be used for right-sided thoracic surgery.