脂肪乳剂不能挽救晚期妊娠大鼠布比卡因诱导的心脏毒性。

Intralipid fails to rescue bupivacaine-induced cardiotoxicity in late-pregnant rats.

作者信息

Sherman Caitlin, Koons Natalie, Zargari Michael, Cha Catherine, Hirsch Jason, Hong Richard, Eghbali Mansoureh, Umar Soban

机构信息

Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United States.

University of New England College of Osteopathic Medicine, Biddeford, ME, United States.

出版信息

Front Med (Lausanne). 2022 Aug 12;9:899036. doi: 10.3389/fmed.2022.899036. eCollection 2022.

DOI:10.3389/fmed.2022.899036

PMID:36035396

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9411664/

Abstract

BACKGROUND

Females routinely receive bupivacaine for obstetric and regional anesthesia. An accidental overdose of bupivacaine can result in cardiotoxicity and cardiac arrest. Intralipid (ILP) rescues bupivacaine-induced cardiotoxicity in male rats. However, bupivacaine cardiotoxicity and ILP rescue have not been studied in non-pregnant and late-pregnant female rats. Here, we tested the hypothesis that an appropriate dose of ILP would rescue non-pregnant and late-pregnant rats from bupivacaine-induced cardiotoxicity.

METHODS

Non-pregnant ( = 6) and late-pregnant ( = 7) female rats received intravenous bupivacaine (10-mg/kg bolus) to induce asystole. Resuscitation with 20% ILP (5-ml/kg actual body weight, single bolus, and 0.5-ml/kg/min maintenance) and chest compressions were continued for 10-min. Serial heart rate (HR), left ventricular ejection-fraction (LVEF%), and LV-fractional shortening (LVFS%) were recorded at baseline and 10-min after bupivacaine-induced cardiac arrest. Data are mean ± SD followed by 95% CI. -values < 0.05 were considered statistically significant.

RESULTS

All rats developed cardiac arrest within a few seconds after bupivacaine. All non-pregnant rats were successfully rescued by ILP, with a HR of 280 ± 32 bpm at baseline vs. 212 ± 18 bpm at 10-min post ILP ( < 0.01), LVEF of 70 ± 6% vs. 68 ± 5% ( = ns), and LVFS of 41 ± 5% vs. 39 ± 4% ( = ns). Interestingly, 6 out of 7 late-pregnant rats did not recover with ILP. Baseline HR, LVEF and LVFS for late-pregnant rats were 330 ± 40 bpm, 66 ± 5% and 38 ± 4%, respectively. At 10-min post ILP, the HR, LVEF, and LVFS were 39 ± 102 bpm ( < 0.0001), 8 ± 22% ( < 0.0001), and 5 ± 12% ( < 0.001), respectively.

CONCLUSIONS

ILP successfully rescued bupivacaine-induced cardiac arrest in non-pregnant rats, but failed to rescue late-pregnant rats.

摘要

背景

女性在产科和区域麻醉中常规使用布比卡因。布比卡因意外过量可导致心脏毒性和心脏骤停。脂质乳剂（ILP）可挽救雄性大鼠布比卡因诱导的心脏毒性。然而，布比卡因心脏毒性和ILP挽救作用尚未在未怀孕和晚孕雌性大鼠中进行研究。在此，我们检验了一个假设，即适当剂量的ILP可挽救未怀孕和晚孕大鼠免于布比卡因诱导的心脏毒性。

方法

未怀孕（n = 6）和晚孕（n = 7）雌性大鼠静脉注射布比卡因（10 mg/kg推注）以诱导心搏停止。用20% ILP（5 ml/kg实际体重，单次推注，0.5 ml/kg/min维持量）进行复苏并持续胸外按压10分钟。在布比卡因诱导心脏骤停的基线和10分钟后记录连续心率（HR）、左心室射血分数（LVEF%）和左心室短轴缩短率（LVFS%）。数据以均数±标准差及95%可信区间表示。P值<0.05被认为具有统计学意义。

结果

所有大鼠在注射布比卡因后数秒内心脏骤停。所有未怀孕大鼠经ILP成功挽救，基线时HR为280±32次/分，ILP后10分钟时为212±18次/分（P<0.01），LVEF为70±6% 对 68±5%（P = 无显著性差异），LVFS为41±5% 对 39±4%（P = 无显著性差异）。有趣的是，7只晚孕大鼠中有6只经ILP未能恢复。晚孕大鼠的基线HR、LVEF和LVFS分别为330±40次/分、66±5%和38±4%。ILP后10分钟时，HR、LVEF和LVFS分别为39±102次/分（P<0.0001）、8±22%（P<0.0001）和5±12%（P<0.001）。