Pretreatment or Resuscitation with a Lipid Infusion Shifts the Dose-Response to Bupivacaine-induced Asystole in Rats
- 1 April 1998
- journal article
- research article
- Published by Wolters Kluwer Health in Anesthesiology
- Vol. 88 (4), 1071-1075
- https://doi.org/10.1097/00000542-199804000-00028
Abstract
The authors sought to confirm a chance observation that intravenous lipid treatment increases the dose of bupivacaine required to produce asystole in rats. The authors also measured the partitioning of bupivacaine between the lipid and aqueous phases of a plasma-lipid emulsion mixture. Anesthetized Sprague-Dawley rats were used in pretreatment (protocol 1) and resuscitation (protocol 2) experiments. In protocol 1, animals were pretreated with saline or 10%, 20%, or 30% Intralipid (n = 6 for all groups), then received 0.75% bupivacaine hydrochloride at a rate of 10 ml x kg x min(-1) to asystole. In protocol 2, mortality was compared over a range of bolus doses of bupivacaine after resuscitation with either saline or 30% Intralipid (n = 6 for all groups). The lipid:aqueous partitioning of bupivacaine in a mixture of plasma and Intralipid was measured using radiolabeled bupivacaine. Median doses of bupivacaine (in milligrams per kilogram) producing asystole in protocol 1 were for 17.7 for saline, 27.6 for 10% Intralipid, 49.7 for 20% Intralipid, and 82.0 for 30% Intralipid (P < 0.001 for differences between all groups). Differences in mean +/- SE concentrations of bupivacaine in plasma (in micrograms per milliliter) were significant (P < 0.05) for the difference between saline (93.3 +/- 7.6) and 30% Intralipid (212 +/- 45). In protocol 2, lipid infusion increased the dose of bupivacaine required to cause death in 50% of animals by 48%, from 12.5 to 18.5 mg/kg. The mean lipid:aqueous ratio of concentrations of bupivacaine in a plasma-Intralipid mixture was 11.9 +/- 1.77 (n = 3). Lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Partitioning of bupivacaine into the newly created lipid phase may partially explain this effect. These results suggest a potential application for lipid infusion in treating cardiotoxicity resulting from bupivacaine.Keywords
This publication has 17 references indexed in Scilit:
- Stereoselective Block of Cardiac Sodium Channels by Bupivacaine in Guinea Pig Ventricular MyocytesCirculation, 1995
- Stereoselective block of a human cardiac potassium channel (Kv1.5) by bupivacaine enantiomersBiophysical Journal, 1995
- Effect of four potassium channel agonists on bupivacaine-induced toxicity in miceLife Sciences, 1995
- Resuscitation from Bupivacaine-Induced Asystole in RatsAnesthesia & Analgesia, 1995
- LEMAKALIM, A POTASSIUM CHANNEL AGONIST, REVERSES ELECTROPHYSIOLOGICAL IMPAIRMENTS INDUCED BY A LARGE DOSE OF BUPIVACAINE IN ANAESTHETIZED DOGSBritish Journal of Anaesthesia, 1993
- Potassium Channel Openers Attenuate Atrioventricular Block by Bupivacaine in Isolated HeartsAnesthesia & Analgesia, 1993
- Effect of Intracerebroventricular Picrotoxin and Muscimol on Intravenous Bupivacaine ToxicityAnesthesiology, 1993
- Effect of Midazolam and Diazepam Premedication on Central Nervous System and Cardiovascular Toxicity of Bupivacaine in PigsAnesthesiology, 1989
- Cardiovascular Toxicity of Local AnestheticsAnesthesia & Analgesia, 1986
- Mechanism for Bupivacaine Depression of Cardiac ConductionAnesthesiology, 1985