◊ BACKGROUND:
Lipid emulsion infusion reverses cardiovascular compromise due to local anesthetic overdose in laboratory and clinical settings. The authors compared resuscitation with lipid, epinephrine, and saline control in a rat model of bupivacaine-induced cardiac toxicity to determine whether lipid provides a benefit over epinephrine.
◊ METHODS:
Bupivacaine, 20 mg/kg, was infused in rats anesthetized with isoflurane, producing asystole in all subjects. Ventilation with 100% oxygen and chest compressions were begun immediately, along with intravenous treatment with 30% lipid emulsion or saline (5-ml/kg bolus plus continuous infusion at 0.5 ml . kg . min) or epinephrine (30 microg/kg). Chest compressions were continued and boluses were repeated at 2.5 and 5 min until the native rate-pressure product was greater than 20% baseline. Electrocardiogram and arterial pressure were monitored continuously and at 10 min, arterial blood gas, central venous oxygen saturation, and blood lactate were measured. Effect size (Cohen d) was determined for comparisons at 10 min.
◊ RESULTS:
Lipid infusion resulted in higher rate-pressure product (P < 0.001, d = 3.84), pH (P < 0.01, d = 3.78), arterial oxygen tension (P < 0.05, d = 2.8), and central venous oxygen saturation (P < 0.001, d = 4.9) at 10 min than did epinephrine. Epinephrine treatment caused higher lactate (P < 0.01, d = 1.48), persistent ventricular ectopy in all subjects, pulmonary edema in four of five rats, hypoxemia, and a mixed metabolic and respiratory acidosis by 10 min.
◊ CONCLUSIONS:
Hemodynamic and metabolic metrics during resuscitation with lipid surpassed those with epinephrine, which were no better than those seen in the saline control group. Further studies are required to optimize the clinical management of systemic local anesthetic toxicity.
◊ Reviewed C. Wu, MD
Associate Professor, Dept. of Anesthesiology and Critical Care Medicine,
The Johns Hopkins School of Medicine, Baltimore, Maryland.
The introduction of the use of intravascular lipid-emulsion therapy for the treatment of local anesthetic-induced cardiovascular collapse has revolutionized the therapeutic options for this potentially devastating complication associated with regional anesthesia. Although the precise mechanism of action is not clear at this time, possible theories include direct metabolic effects on cardiac myocytes or indirect effects acting as a circulating lipid 'sink' that absorbs excess local anesthetic[1]. Despite the uncertainty regarding the mechanism of action, several clinical reports have noted the rapid and successful reversal of local anesthetic-induced cardiovascular collapse with the administration of lipid emulsion. In addition, administration of lipid emulsion may reverse local anesthetic-induced cardiac dysrhythmias and central nervous system effects.
Epinephrine still remains a first-line treatment of cardiac arrest in general; however, its efficacy (versus lipid emulsion) for the treatment of local anesthetic-induced cardiovascular collapse has not been examined. Furthermore patients with local anesthetic-induced cardiovascular collapse may be resistant to epinephrine therapy and may develop pulmonary edema as a result of such treatment [2].
In this study using a rodent model of bupivacaine overdose, the authors demonstrated that lipid-emulsion therapy resulted in an improved recovery profile (cardiovascular parameters, arterial blood gases, serum lactate levels) compared to epinephrine-based resuscitation or saline infusion. In addition, a majority of rats randomized to receive epinephrine had pulmonary edema which contributed to the poor outcome in this group. It should be noted that a recent study authored by this group also noted that vasopressin (compared to lipid emulsion) appears to be unfavorable for resuscitation from local anesthetic toxicity [3].
Although the results of this study superficially suggest that lipid emulsion is superior to epinephrine in the treatment of local anesthetic-induced cardiovascular collapse, there are several caveats in extrapolating this data into clinical practice. The results should not be interpreted that the use of epinephrine should be completely abandoned in favor of lipid emulsion therapy. The study was performed in animals and whether similar results can be obtained in humans is uncertain. Finally, long-term outcomes (e.g., survival, neurologic injury) were not assessed. Thus, translating the results of this animal study to clinical practice should be made with extreme caution.
Nevertheless, use of intravascular lipid-emulsion therapy for the treatment of local anesthetic-induced cardiovascular collapse should be considered as a front-line treatment option. Recent case reports have found that intravascular lipid-emulsion therapy may also be effective for the treatment of other types of overdose including selective central serotonin reuptake inhibitors [4]. Updated information on the use of lipid emulsion in this context can be found on Dr. Weinberg’s website [http://lipidrescue.org/].
◊ References
1. Picard J, Harrop-Griffiths W.
Lipid emulsion to treat drug overdose: past, present and future. Anaesthesia 2009 Feb;64(2):119-21.
2. Reinikainen M, Hedman A, Pelkonen O, Ruokonen E.
Cardiac arrest after interscalene brachial plexus block with ropivacaine and lidocaine. Acta Anaesthesiol Scand 2003 Aug;47(7):904-6.
3. Di Gregorio G, Schwartz D, Ripper R, Kelly K, Feinstein DL, Minshall RD, Massad M, Ori C, Weinberg GL
Lipid emulsion is superior to vasopressin in a rodent model of resuscitation from toxin-induced cardiac arrest. Crit Care Med 2009 Mar;37(3):993-9.
4. Finn SD, Uncles DR, Willers J, Sable N.
Early treatment of a quetiapine and sertraline overdose with Intralipid. Anaesthesia 2009 Feb;64(2):191-4. |
