Anesthesia and analgesia
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Anesthesia and analgesia · Apr 1998
Randomized Controlled Trial Comparative Study Clinical TrialThe pharmacokinetics of acetyl starch as a plasma volume expander in patients undergoing elective surgery.
Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase 2 clinical trials. We compared the pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients (ASA physical status I and II) undergoing elective surgery. In this randomized, double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular weight [Mw] 200,000/molar substitution [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximal dose of 1000 mL. Plasma colloid concentrations were measured by repetitive arterial blood sampling over 24.5 h. Plasma colloid concentrations were detected using a high-pressure liquid chromatography controlled enzymatic test. Standard pharmacokinetics were calculated, including initial half-life (t(1/2init)), i.e., the time required for a 50% decline of the maximal plasma colloid concentration at the end of drug infusion. Whereas HES was eliminated by second-order kinetics, ACS followed first-order characteristics. In the first hours after i.v. administration, t(1/2init) and clearances were similar in both groups. However, the terminal half-life of HES was significantly longer than that of ACS (9.29 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed significantly lower plasma concentrations than HES, which indicates that the final degradation of ACS by esterases and amylase was significantly more rapid. ACS might be an alternative plasma volume expander, which avoids the accumulation of persisting macromolecules. ⋯ We studied the pharmacokinetics of acetyl starch, a newly developed colloid solution for plasma volume substitution, compared with hydroxyethyl starch in 32 surgical patients undergoing elective major general surgical procedures. In contrast to hydroxyethyl starch, this new agent undergoes rapid and nearly complete enzymatic degradation.
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Anesthesia and analgesia · Apr 1998
Systemic and regional pharmacokinetics of levobupivacaine and bupivacaine enantiomers in sheep.
Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)-bupivacaine. S(-)-bupivacaine (levobupivacaine) is the subject of current clinical evaluation. We conducted partial cross-over systemic and regional pharmacokinetic studies of i.v. bupivacaine (12.5-200 mg) and levobupivacaine (6.25-200 mg) in ewes. Enantiospecific analysis of blood drug concentration-time data and of regional myocardial and brain drug mass balance data indicated that (a) there was a higher mean total body clearance of R(+)-bupivacaine than of S(-)-bupivacaine (as previously reported); (b) there were no differences in the systemic pharmacokinetics of S(-)-bupivacaine whether administered alone or as a component of bupivacaine; (c) there was no evidence of dose-dependent pharmacokinetics with either enantiomer; (d) for both enantiomers, mean calculated myocardial tissue concentrations of 1%-4% dose occurred between 3 and 5 min. Mean brain concentrations of 0.2%-1% dose occurred between 2 and 4 min after the administration of bupivacaine but between 4 and 5 min after the administration of levobupivacaine. There was no evidence that systemic toxicity induced by these local anesthetics significantly modified their pharmacokinetics, and there was no evidence of an enantiomer-enantiomer pharmacokinetic interaction for bupivacaine. ⋯ Levobupivacaine comprises 50% of commercially available bupivacaine and is being considered for use in its own right. As a part of its preclinical evaluation, this study considered whether levobupivacaine behaved kinetically in the body in the same way as when administered as a component of bupivacaine.
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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
Inhaled prostaglandin E1 for treatment of acute lung injury in severe multiple organ failure.
Acute lung injury is characterized by hypoxemia due to pulmonary ventilation/perfusion-mismatching. I.v. administered prostaglandin E1 (PGE1), a vasodilator with a high pulmonary clearance, has been studied in acute lung injury. Inhalation of the vasodilators nitric oxide and prostacyclin improved oxygenation by selective dilation of the pulmonary vasculature in ventilated lung areas. In the present study, PGE1 inhalation was used for treatment of acute lung injury. Fifteen patients with acute lung injury defined as PaO2/fraction of inspired oxygen (FIO2) <160 mm Hg were treated with PGE1 inhalation in addition to standard intensive care. The drug was continuously delivered via a pneumatic nebulizer. Acute physiology and chronic health evaluation system II and multiple organ failure scores were (mean +/- SEM) 33 +/- 2 and 10 +/- 0.3, respectively. Inhaled PGE1 was administered for 103 +/- 17 h at a dose of 41 +/- 2 microg/h. The PaO2/FIO2 ratio increased from 105 +/- 9 to 160 +/- 17 mm Hg (P < 0.05) and to 189 +/- 25 mm Hg (P < 0.05) after 4 h and 24 h, respectively. PGE1 inhalation decreases in mean pulmonary artery pressure and central venous pressure were not statistically significant. Mean arterial pressure, pulmonary capillary wedge pressure, cardiac output, and heart rate remained unchanged. Intensive care unit mortality was 40%. The present data suggest that inhaled PGE1 is an effective therapeutic option for improving oxygenation in patients with acute lung injury. Whether inhaled PGE1 will increase survival in acute lung injury should be investigated in a controlled prospective trial. ⋯ In patients with severe acute lung injury and multiple organ failure, inhaled prostaglandin E1 improved oxygenation and decreased venous admixture without affecting systemic hemodynamic variables. Controlled clinical trials are warranted.