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

Abstract

<jats:p> Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid<jats:sup>®</jats:sup> ( n = 7) with Ringer’s acetate ( n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer’s acetate administration ( p &lt; 0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid ( p &lt; 0.05) but unaffected by Ringer’s acetate. The mean (standard deviation) area under the concentration–time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg·min/L) than after Ringer’s acetate (88.1 (7.1) mg·min/L) ( p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg·min/L) was 8% lower than that of total bupivacaine ( p &lt; 0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function. </jats:p>

Lipid Emulsion Inhibits the Late Apoptosis/Cardiotoxicity Induced by Doxorubicin in Rat Cardiomyoblasts

“…Combined treatment with lipid emulsion and bupivacaine increases the MMP more than bupivacaine alone [ 29 ]. In addition, the mitochondrial respiratory function in the cardiac depression induced by bupivacaine is enhanced by lipid emulsion [ 41 ]. Consistent with these previous reports, doxorubicin decreased the MMP in H9c2 rat cardiomyoblasts, whereas lipid emulsion reversed the attenuated MMP induced by doxorubicin ( Figure 6 ) [ 29 , 40 ].…”

Lipid Emulsion for Treating Local Anesthetic Systemic Toxicity

“…These previous reports suggest that lipid emulsion-mediated recovery from bupivacaine-induced cardiac toxicity was associated with the reversal of the reduced fatty acid supply and ATP production or the mitochondrial dysfunction induced by toxic doses of bupivacaine 49 - 52 . In another study, lipid emulsion enhanced the mitochondrial respiratory function of myocardial cells and produced slight bupivacaine entrapment in bupivacaine-induced cardiac depression of pigs 53 . However, lipid emulsion did not improve the bupivacaine-induced decreased cardiac index 53 .…”

The effect of 50% compared to 100% inspired oxygen fraction on brain oxygenation and post cardiac arrest mitochondrial function in experimental cardiac arrest

“…Using PbO2 values from a previous study (intra-arrest PbO2 with 100% oxygen of 5±3.5 mmHg) a study with nine animals in each group would be needed to show equivalence between interventions. 16 Regarding, the mitochondrial analysis using baseline data on mitochondrial respiration after succinate addition 15 and assuming a 40% decrease overall in function with CA 11 , four animals would be needed per group to show a 40% difference between the 50% and 100% FiO2 groups. Given risk of technical failures we increased the total sample size to ten per group with five mitochondrial samples per groups.…”

“…14 The oxygen flux was measured using a previously described fatty acid substrate uncouplerinhibitor titration protocol, with a slight modification in the injection order. 11,15 The mitochondrial analysis is presented in detail in the ESM.…”