Intravenous Lipid Emulsion for Levobupivacaine Intoxication in Acidotic and Hypoxaemic Pigs

Abstract

Intravenous lipid emulsion is, in some countries, the recommended treatment for local anaesthetic toxicity. Systemic local anaesthetic toxicity results in hypoxaemia and acidosis, and whether this influences the effects of lipid therapy on drug concentrations and cardiovascular recovery is currently unknown. Twenty anaesthetised pigs were given a 3 mg/kg bolus of levobupivacaine followed by a five-minute phase of hypoventilation and 1 mmol/kg of lactic acid over one minute. After lactic acid infusion, pigs were treated, in randomised order, with either 20% lipid emulsion or Ringer's acetate for 30 minutes: a 1.5 ml/kg bolus followed by a 0.25 ml/kg/minute infusion. Haemodynamic parameters were recorded and blood samples were collected for pharmacokinetic analysis. There was no difference between the groups in the area under the plasma levobupivacaine concentration-time curve (AUC) or between that and AUC of unentrapped levobupivacaine in the Lipid group, or in the plasma half-lives. The cardiovascular outcome and normalisation of the electrocardiogram were similar in both groups. Five pigs developed marked hypotension: one in both groups died, while two in the Lipid group and one in the Ringer group needed adrenaline. Administration of lipid emulsion did not improve cardiovascular recovery from levobupivacaine toxicity exacerbated by acidosis and hypoxaemia. Lipid emulsion did not entrap levobupivacaine or affect levobupivacaine pharmacokinetics.

The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs

“…In our previous studies in pigs and humans 8,[37][38][39] with the internationally recommended clinical rescue dose of lipid emulsion, 3 we could not demonstrate any relevant entrapment of bupivacaine or other local anesthetics in the plasma lipid phase. In the present study with the high 4 mL/kg bolus dose of lipid emulsion, the un-entrapped bupivacaine concentration, measured in the plasma aqueous phase, was about 8% lower than its total concentration.…”

Lipid Rescue – Efficacy and Safety Still Unproven

“…Notably, many of the reports of such studies originate from one research group . An increasing number of controlled animal studies have not, however, reported positive effects of this therapy in LAST . Several experimental studies on the presumed beneficial effect of lipid rescue on the toxicity of other drugs than local anaesthetics have been negative or shown the opposite effect .…”