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Giving Priority to Lipid Administration Can Reduce Lung Injury Caused by Epinephrine in Bupivacaine-Induced Cardiac Depression
  1. Mengxu Luo, MD*,
  2. Xia Yun, MD, PhD,
  3. Chaoxing Chen, BS*,
  4. Nana Bao, BS*,
  5. Xiaona Feng, BS*,
  6. Linmin Pan, BS*,
  7. Zhousheng Jin, MD*,
  8. Cong Wu, BS*,
  9. Xianqin Wang, PhD,
  10. Thomas J. Papadimos, MD, MPH and
  11. Xuzhong Xu, MD*
  1. From the *Department of Anesthesiology, First Affiliated Hospital, Wenzhou Medical University, Zhejiang, China; †Department of Anesthesiology, the Ohio State University Medical Center, Columbus, OH; and ‡Analysis and Testing Center, Wenzhou Medical University, Zhejiang, China
  1. Address correspondence to: Xuzhong Xu, MD, Department of Anesthesiology, the First Affiliated Hospital, Wenzhou Medical University, Shangcaivillage, Nanbaixiang, Ouhai, Wenzhou, Zhejiang, China 325000 (e-mail: xuzhong{at}


Background and Objectives Epinephrine is usually administered in concert with a lipid emulsion during local anesthetic toxicity. However, the timing and role of epinephrine administration in combination with a lipid emulsion remain unclear. Specifically, the temporal association of epinephrine and lipid emulsion administration with related changes in pulmonary vascular pressures that may lead to pulmonary edema and hemorrhage needs to be determined.

Methods This study consisted of 2 parts, experiments A and B. In experiment A, 24 adult male Sprague-Dawley rats were randomly divided into 3 groups (n = 8) to receive 1 of 3 treatments. All rats were anesthetized with an intraperitoneal injection of chloral hydrate, and anesthesia was maintained by sevoflurane. Each treatment group was initially given an infusion of bupivacaine (15 mg/kg) in order to produce cardiac depression. Group 1 (A-LEN) received a 30% lipid infusion (3 mL/kg) followed by a rapid epinephrine bolus (10 μg/kg), which was then followed by a normal saline infusion (3 mL/kg). Group 2 (A-NEL) first received a normal saline infusion (3 mL/kg) followed by a rapid epinephrine bolus, which was then followed by a 30% lipid emulsion. Group 3 (A-NEN, considered a control group) first received a normal saline infusion (3 mL/kg) followed by a rapid epinephrine bolus (10 μg/kg), which was then followed by another normal saline infusion (3 mL/kg). Lipid and normal saline infusions were administered over 1 minute, whereas epinephrine was injected rapidly. The continuous monitoring of blood pressure, heart rate, pulmonary arterial pressure, and pulmonary venous pressure occurred for 30 minutes. After the 30-minute monitoring period, lung tissue was sampled, and bronchoalveolar lavage fluid was collected. In experiment B, the experimental model and resuscitation protocol were similar to experiment A (B-LEN and B-NEL groups). In this arm of the experiment, bupivacaine concentrations of cardiac tissue were determined after the second minute of normal saline infusion.

Results The A-LEN group produced the best rate pressure product when compared with the A-NEL or A-NEN group (P = 0.045, P = 0.011, respectively). In regard to pulmonary venous pressure, the A-LEN group was lower than the A-NEL or A-NEN group (P = 0.031, P = 0.006, respectively). Animals in the A-NEL and A-NEN groups rapidly developed pulmonary edema after infusion of epinephrine. The wet-to-dry ratio of the lungs in the A-LEN group was lower than that of the lungs in the A-NEL group (P = 0.024).The lung permeability index of the A-LEN group was lower than that of the A-NEL group (P = 0.011). In experiment B, concentrations of bupivacaine in cardiac tissue and plasma of the B-LEN group were lower than those of the B-NEL group (P = 0.001, P = 0.03, respectively).

Conclusions Giving priority to the administration of a lipid emulsion before the administration of epinephrine can reduce lung injury in bupivacaine-induced cardiac depression in rats.

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  • The authors declare no conflict of interest.

    This work was supported by an international collaboration project from the Science Technology Department of Zhejiang Province, China (no. 2012c24018). The project was also supported by the Natural Science Foundation of Zhejiang Province, China (no. LY13HO90008).