Hemodynamic Effects of Intravenous, High‐Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial

Abstract

In a double-blinded, randomized, crossover trial, we investigated the hemodynamic effects of high-dose intravenous lipid emulsion (ILE) with/without metoprolol. Ten healthy volunteers each completed 4 trial days (placebo + ILE; metoprolol + placebo; metoprolol + ILE; placebo + placebo) in random order. Metoprolol was administered as an initial bolus (10 mg), followed by an infusion (50 mg) from 5 to 30 minutes. ILE was administered as a bolus at 12.5 minutes (2.5 mL/kg), followed by a 15-minute infusion (0.25 mL/kg per minute). On metoprolol + ILE days (compared with metoprolol + placebo) after 120 minutes, mean heart rates were significantly higher (difference, 5.5 beats per minute (bpm); 95% confidence interval (CI), 3.0-8.1 bpm; P < 0.001), and average relative cardiac output was higher (difference, 10 percentage points; 95% CI, 5-15 percentage points; P < 0.001). The hemodynamic effect of ILE developed gradually. ILE had no effect on plasma metoprolol or major adverse events. In conclusion, high-dose ILE has relatively marginal and delayed hemodynamic effects that may have limited clinical relevance in the shortterm clinical toxicological setting.Administration of intravenous lipid emulsion (ILE) for hemodynamic stabilization in conditions of systemic toxicity caused by local anesthetics is recommended by anesthetic and toxicological scientific societies. 1-3 Recommendations are primarily based on findings from animal studies and clinical case reports. 4 Proposed mechanisms behind possible hemodynamic stabilizing effects of ILE include binding of the drug in the plasma lipid phase, which may provide a beneficial redistribution effect, 5 volume effects, and cardiotonic effects. 6 The American College of Medical Toxicology also regards ILE as

Lipid emulsion for xenobiotic overdose: PRO

“…Nevertheless, volunteer studies of subtoxic doses confirm the mechanistic benefit of ILE in bupivacaine, 32 ropivacaine, levobupivacaine 33 and lidocaine 55 . Further, RCTs have emerged in the setting of non‐LAST, 56–63 specifically demonstrating a clinical benefit of ILE in poisoning from pesticides, 57–60 antipsychotics (primarily clozapine), 61,62 tramadol 63 and metoprolol 64 . There are several conclusions to be drawn from these clinical trials 56–63 and volunteer studies 32,33,55,64 (Table 1).…”

“…Log D at pH 7.4) (Figure 2A,B). Following on this dose assertion, the clinical benefit of ILE may extend beyond lipophilic substances as demonstrated by the clinical trials of metoprolol 64 and aluminium phosphide 59 . Finally, many trials originate from developing countries afflicted by high rates of toxicity from pesticides and antipsychotics.…”

“…55 Further, RCTs have emerged in the setting of non-LAST, [56][57][58][59][60][61][62][63] specifically demonstrating a clinical benefit of ILE in poisoning from pesticides, [57][58][59][60] antipsychotics (primarily clozapine), 61,62 tramadol 63 and metoprolol. 64 There are several conclusions to be drawn from these clinical trials [56][57][58][59][60][61][62][63] and volunteer studies 32,33,55,64 (Table 1). First, ILE causes minimal complications.…”

“…As stated above, recent clinical trials [57][58][59][60][61][62][63][64] report infrequent and mild complications (e.g. irritation at injection site).…”

“…99 This recommendation not only neglects a century of experience in the anaesthesia community that pressor-based resuscitation is ineffective in LAST 14,15 but also ignores the recommendations from professional anaesthesia societies 20,21 and directly contradicts quantitative meta-analysis of data presented in the LEW's own publications. 48,49 Beyond LAST, emerging human models suggest the utility of ILE in pesticide, [57][58][59][60] antipsychotics (primarily clozapine), 61,62 tramadol 63 and metoprolol 64 toxicities, outdating the LEW's strong recommendation of 'not using ILE … as part of treatment modalities" 99 for beta-blocker toxidromes and calling into question their recommendation of 'not using ILE as first-line therapy' for many others.…”