Resuscitation with Lipid Emulsion

Abstract

Background Recent publications have questioned the validity of the “lipid sink” theory of lipid resuscitation while others have identified sink-independent effects and posed alternative mechanisms like hemodilution. To address these issues, we tested the dose-dependent response to intravenous lipid emulsion during reversal of bupivacaine-induced cardiovascular toxicity in vivo. Subsequently, we modeled the relative contribution of volume resuscitation, drug sequestration, inotropy and combined drug sequestration and inotropy to this response using an in silico model. Methods Rats were surgically prepared to monitor cardiovascular metrics and deliver drugs. Following catheterization and instrumentation, animals received a nonlethal dose of bupivacaine to produce transient cardiovascular toxicity, then were randomized to receive one of four treatments: 30% or 20% intravenous lipid emulsion, intravenous saline or no treatment (n = 7 per condition; 28 total animals). Recovery responses were compared to the predictions of a pharmacokinetic-pharmacodynamic model parameterized using previously published laboratory data. Results Rats treated with lipid emulsions recovered faster than did rats treated with saline or no treatment. Intravenous lipid emulsion of 30% elicited the fastest hemodynamic recovery followed in order by 20% intravenous lipid emulsion, saline, and no-treatment. An increase in arterial blood pressure underlay the recovery in both lipid-emulsion treated groups. Heart rates remained depressed in all four groups throughout the observation period. Model predictions mirrored the experimental recovery and the model that combined volume, sequestration and inotropy predicted in vivo results most accurately. Conclusion Intravenous lipid emulsion accelerates cardiovascular recovery from bupivacaine toxicity in a dose-dependent manner, driven by a cardiotonic response that complements the previously reported sequestration effect.

Part 10: Special Circumstances of Resuscitation

“…131 Administration of ILE also increases cardiac inotropy by other mechanisms. [132][133][134] Over time, common use of this modality has been expanded to include poisoning by other local anesthetics and other medications. [135][136][137][138] The 2015 ILCOR systematic review addressed the question of whether administration of lipid emulsion improves outcomes for patients who develop cardiac arrest due to drug toxicity, including that caused by local anesthetics and other drugs.…”

Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

“…We injected H 3 -radiolabeled drug intravenously in anesthetized rats at a dose that produces transient asystole recoverable without intervention [30,33]; recovery was monitored with or without ILE intervention (10mL/kg 30% Intralipid® delivered intravenously over 1 minute). Treatment with ILE accelerated cardiovascular recovery (Fig.…”

“…Solution of the resulting differential equations predicts the time course of cardiac failure and lipid-mediated resuscitation as a function of hypothesized mechanism of therapeutic action. The results reported herein were obtained using an augmented version of the model described in reference [30]. Modifications made include: (i) adjustment of the lipid delivery timeline to correspond with the in vivo experiments; and (ii) incorporation of a non-competitive inhibition model for the interplay between bupivacaine toxicity and the cardiotonic effect of the lipid.…”

“…We recently demonstrated that a micro-emulsion of triglycerides produces an inotropic effect in the absence of toxicity [29], and further proposed that this effect coupled with the volume load is necessary for full recovery from cardiac pharmacotoxicity [30]. The prominent role of a non-scavenging effect in recovery and the ability of fatty-acid oxidase inhibitors to block emulsion-based recovery from pharmacotoxicity [31] call into question whether scavenging is relevant to recovery.…”

Lipid Emulsion Rapidly Restores Contractility in Stunned Mouse Cardiomyocytes

“…Recently, there has been a renewed interest in the potential for ILE infusion to activate traditional cardio-protective pathways following stunning (13, 14) because of its success in treating cardiac pharmacotoxicity (40) partially through an improvement in contractility (41). Previous experiments have described a benefit of ILE on the recovery from ischemic damage in patients (15), conscious dogs (16), isolated rabbit hearts (17) and isolated rat hearts (13, 14, 29, 42) when delivered at reperfusion.…”