Lidocaine preferentially inhibits the function of purinergic P2X7 receptors expressed in Xenopus oocytes.

BACKGROUND: Lidocaine has been widely used to relieve acute pain and chronic refractory pain effectively by both systemic and local administration. Numerous studies reported that lidocaine affects several pain signaling pathways as well as voltage-gated sodium channels, suggesting the existence of multiple mechanisms underlying pain relief by lidocaine. Some extracellular adenosine triphosphate (ATP) receptor subunits are thought to play a role in chronic pain mechanisms, but there have been few studies on the effects of lidocaine on ATP receptors. We studied the effects of lidocaine on purinergic P2X3, P2X4, and P2X7 receptors to explore the mechanisms underlying pain-relieving effects of lidocaine. METHODS: We investigated the effects of lidocaine on ATP-induced currents in ATP receptor subunits, P2X3, P2X4, and P2X7 expressed in Xenopus oocytes, by using whole-cell, two-electrode, voltage-clamp techniques. RESULTS: Lidocaine inhibited ATP-induced currents in P2X7, but not in P2X3 or P2X4 subunits, in a concentration-dependent manner. The half maximal inhibitory concentration for lidocaine inhibition was 282 ± 45 µmol/L. By contrast, mepivacaine, ropivacaine, and bupivacaine exerted only limited effects on the P2X7 receptor. Lidocaine inhibited the ATP concentration-response curve for the P2X7 receptor via noncompetitive inhibition. Intracellular and extracellular N-(2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX-314) and benzocaine suppressed ATP-induced currents in the P2X7 receptor in a concentration-dependent manner. In addition, repetitive ATP treatments at 5-minute intervals in the continuous presence of lidocaine revealed that lidocaine inhibition was use-dependent. Finally, the selective P2X7 receptor antagonists Brilliant Blue G and AZ11645373 did not affect the inhibitory actions of lidocaine on the P2X7 receptor. CONCLUSIONS: Lidocaine selectively inhibited the function of the P2X7 receptor expressed in Xenopus oocytes. This effect may be caused by acting on sites in the ion channel pore both extracellularly and intracellularly. These results help to understand the mechanisms underlying the analgesic effects of lidocaine when it is administered locally at least.

[Investigation of the amount of blood loss in patients with ruptured and unruptured ectopic pregnancies: a 3-year comparative study].

BACKGROUND: Anesthesiologists should carefully monitor clinical symptoms and hemodynamics of ectopic pregnant patients. METHODS: We retrospectively investigated the backgrounds, vital signs, and amount of blood loss during surgery of ectopic pregnant patients who visited our hospital between July 2009 and June 2012. RESULTS: Ultrasonic examinations revealed a ruptured ectopic pregnancy (REP) in 17 patients and unruptured ectopic pregnancy (UEP) in 19 patients. All operations were uneventful. One UEP patient became hemodynamically unstable immediately after arriving at the operating room because of a sudden rupture. The differences in patients' ages, heights, weights, gestational ages, and human chorionic gonadotropin levels were not statistically significant between the REP and UEP groups. Clinical symptoms (abdominal pain or atypical genital bleeding) were observed in 14 of 17 REP patients and in 5 of 19 UEP patients (relative risk 3.1, odds ratio 13.1). The amount of blood loss was 79 g in the UEP patients, 356 g in the 14 hemodynamically stable REP patients, and 1,762 g in the 3 hemodaynamically unstable REP patients. The clinical symptoms were related to the existence of ruptures. CONCLUSIONS: It is important to monitor clinical symptoms in addition to hemodynamics for sudden hemodynamic changes in ectopic pregnancy.

[Insufficient sugammadex effect in an obese pregnant woman undergoing cesarean section under general anesthesia].

A 32-year-old pregnant woman (height 162 cm, weight 86 kg, age of fetus 25 weeks) without preoperative complications underwent an emergent cesarean section under general anesthesia. She was intubated with a 7.0-mm tracheal tube 40 s after receiving rocuronium 0.93 mg x kg(-1) and thiamilal 375 mg. Anesthesia was maintained with oxygen, air, sevoflurane 1.0-2.5%, and fentanyl 425 microg. Nine minutes after the end of surgery (operation time 71 minutes), a train-of-four count of 2 with 20 spontaneous breaths was noted, and sugammadex 2.3 mg x kg(-1) was administered. However, the train-of-four count was 3 even five minutes after sugammadex administration. Fifteen minutes after sugammadex administration (train-of-four ratio 14%), she received atropine 0.5 mg and neostigmine 1.0 mg. Ten minutes later, the train-of-four ratio increased to 89%, and the patient was successfully extubated with no respiratory suppression. We speculate that the rocuronium dose (0.93 mg x kg(-1)) was too high in this obese patient, and sugammadex dose at the end of the surgery was not enough for reversal of rocuronium-induced neuromuscular blockade.