◊ BACKGROUND:
Lipid emulsion infusion reverses local anesthetic-induced cardiac toxicity, but the effect of adding epinephrine has not been studied. We compared escalating doses of epinephrine on recovery with lipid infusion in a rat model of bupivacaine overdose.
◊ METHODS:
Rats anesthetized with isoflurane received an IV bolus of 20 mg/kg bupivacaine, producing asystole (zero time) in all animals. Ventilation (100% oxygen) and chest compressions were started immediately, and at 3 min the rats received one of six IV treatments (n = 5 for all groups): 5 ml/kg saline followed by infusion for 2 min at 1.0 ml · kg-1 · min-1, and a second 5 ml/kg bolus at 5 min; or the same bolus and infusion treatment using 30% lipid emulsion plus a single injection of epinephrine at one of five doses: 0 (lipid control), 1, 2.5, 10, or 25 mcg/kg. An electrocardiogram and arterial pressure were monitored continuously, and arterial blood gas was measured at 7.5 and 15 min.
◊ RESULTS:
Epinephrine improved initial return of spontaneous circulation (rate-pressure product > 30% baseline) but only 3 of 5 rats at 10 mcg/kg and 1 of 5 rats at 25 mcg/kg sustained return of spontaneous circulation by 15 min. Lipid alone resulted in slower but more sustained recovery. Epinephrine doses above a threshold near 10 mcg/kg increased lactate, worsened acidosis, and resulted in poor recovery at 15 min, as compared with lipid controls. There was tight correlation of epinephrine dose to serum lactate at 15 min.
◊ CONCLUSIONS:
Epinephrine over a threshold dose near 10 mcg/kg impairs lipid resuscitation from bupivacaine overdose, possibly by inducing hyperlactatemia.
◊ Reviewed by P. Rosenberg MD. PhD.
Professor of Anaesthesiology
Department of Anaesthesiology and Intensive Care Medicine, Meilahti Hospital, Helsinki University Hospital, Helsinki, Finland
It is difficult to translate presented data from studies in rats to the clinical situation. In the first place, the dose of the lipid emulsion administered to the rats was huge, i.e. 12 ml/kg intravenously for the 30%-lipid emulsion. Extrapolated to a 70 kg man, it would equal 840 ml (252 g).
The safety of such high and rapidly (within 160 seconds) administered doses of lipid emulsion has not been established. Significant side effects of the lipid infusion are possible and may even be expected. The pharmacopoeias present long lists of possible serious acute side effects, such as thrombophlebitis, allergic reactions, hypercoagulability, hyperpyrexia, and dizziness. Already in 1987, it was shown that rapid experimental infusions of large doses of Intralipid cause pulmonary hypertension in lambs and a significant rise in thromboxane B2 [1].
On the other hand, in this rat study the two smallest and “safe” epinephrine doses of 1 and 2.5 µg/kg were below the clinical dose range of 0.5 to 1 mg in cardiopulmonary resuscitation. For an adult of 70 kg of weight, this range corresponds to approximately 7 to 14 µg/kg. Thus, the two higher doses of 10 and 25 µg/kg which impaired recovery in the present rat study can be considered relevant to the clinical situation. These doses of epinephrine together with the lipid emulsion caused marked lactatemia and metabolic acidosis, including poor outcome of resuscitation. This may not be surprising given the probability of a concomitant inflammatory and constrictive vascular response to the massive lipid emulsion exposure.
Finally, extrapolation from rat to man of haemodynamic data of cardiopulmonary resuscitation after local anaesthetic-induced cardiac arrest may not be relevant unless postresuscitative cognitive function of the experimental animals is explored. Thus, one concurs with the final conclusion of the authors that further studies are needed.
◊ References:
[1] Teague WG Jr, Raj JU, Braun D, Berner ME, Clyman RI, Bland RD. Lung vascular effects of lipid infusion in awake lambs. Pediatr Res 1987;22:714-719.
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