Background
Pregnant patients routinely get neuraxial anesthesia for labor and delivery. Bupivacaine is one of the most commonly used local anesthetics in obstetric anesthesia. Some laboratory studies have suggested that pregnancy increases the cardiotoxicity of Bupivacaine. We have previously shown that Intralipid (ILP) rescues the heart from Bupivacaine-induced cardiotoxicity in male rats. However, Bupivacaine cardiotoxicity and ILP rescue have not been extensively studied in pregnant rats. We aimed to investigate the cardiotoxicity of Bupivacaine and the potential of ILP’s rescue in pregnant rats.
Methods
Pregnant female rats (200-350g, n=5) were used for the study. Rats were anesthetized intraperitoneally with a mixture of Ketamine (80 mg/kg) and Xylazine (8 mg/kg). Tracheostomy was performed using a 16-gauge angio-catheter and rats were ventilated with a ventilator. Femoral vein was accessed through a 24-gauge intravenous catheter. Body temperature was maintained at 37°C. Rats received Bupivacaine bolus (10 mg/kg, IV over ~20 seconds) to induce asystole. Resuscitation with ILP 20% (5 ml/kg bolus, and 0.5 ml/kg/min maintenance) and chest compressions were initiated. Serial B-Mode and M-Mode transthoracic echocardiography was continuously performed using a VisualSonics Vevo 2100 system equipped with a 30-MHz linear transducer. Standard Lead II Electrocardiograms were acquired under anesthesia continuously throughout the experiment. The ejection-fraction (EF%), fractional shortening (FS%), and heart rate (HR, beats per min) were calculated at baseline and at 1, 5, and 10 minutes after ILP treatment.
Results
All five rats developed cardiac arrest within a few seconds after a toxic dose of Bupivacaine. Interestingly, only 2 out of the 5 rats were rescued with ILP using the usual rescue dose typically used in male rats. Baseline EF and HR were 66.30±2.99% and 310±34 bpm respectively. One minute after ILP, EF and HR were 38.24% and 143 bpm. Five minutes after ILP, EF and HR were 57.62% and 227 bpm. Ten minutes after ILP, EF and HR were 59.49% and 270 bpm. In the no recovery with intralipid group of rats (n=3) the average baseline EF and HR were 69.28±0.57% and 331±65 bpm. Ten minutes after ILP, EF and HR were 0.
Conclusions
ILP unreliably rescued Bupivacaine-induced cardiac arrest in pregnant rats. More experiments are needed to find out the optimal rescue dosage regimen of ILP for Bupivacaine-induced cardiac arrest in pregnant rats. Physiologic changes associated with pregnancy, sensitivity to Bupivacaine, pregnancy-induced heart hypertrophy and changes in cardioprotective signaling cascades may be responsible for the unreliable rescue of Bupivacaine cardiotoxicity by ILP in pregnancy.
