Systemic Lidocaine or Mexiletine for Neuropathic Pain

Clinical Question

When used systemically, are lidocaine (Xylocaine) and its oral analogue mexiletine (Mexitil) safe and effective for the treatment of neuropathic pain?

Evidence-Based Answer

Intravenous lidocaine and oral mexiletine provide a modest reduction in neuropathic pain with no indication of serious adverse effects. However, safety data are limited because most studies were of relatively short duration and fewer than 400 patients have been studied in total for each drug. Intravenous lidocaine and oral mexiletine should be considered second- or third-line options for the treatment of neuropathic pain and should be given only after a careful discussion with the patient regarding risks and benefits.

Practice Pointers

Case reports from the 1950s suggest that intravenous lidocaine, typically used as a local anesthetic, could provide pain relief in patients with cancer or postoperative pain. Subsequent reports in the 1980s suggested a similar benefit for the oral analogues mexiletine, flecainide (Tambocor), and tocainide (Tonocard). In the past decade, several better-designed clinical trials have been published; this Cochrane review provides an update on the safety and efficacy of lidocaine and its oral analogue mexiletine for the systemic treatment of neuropathic pain.

The authors reviewed randomized, double-blind, controlled studies that involved patients with neuropathic pain, including peripheral neuropathy, regional pain syndromes, spinal cord injury, trigeminal neuralgia, phantom limb pain, and fibromyalgia. Of the 30 studies identified, 12 were of good methodologic quality and all were small (median number of participants 28, range 8 to 87). The amount of intravenous lidocaine typically infused was between 1 and 5 mg per kg.

In 11 studies of lidocaine with a total of 373 patients, the researchers found a mean reduction of 11 mm in a 100-mm visual pain scale (95% confidence interval [CI], −17 to −5). The same benefit (mean difference −11 mm, 95% CI, −16 to −6) was found in nine studies of oral mexiletine (median dosage 600 mg per day for a median of nine weeks) with a total of 377 patients. Results generally were consistent and of similar magnitude among studies. Although statistically significant, an 11-mm improvement on a 100-mm scale generally is felt to be of borderline clinical significance. Adverse events (none serious) were more common in patients receiving lidocaine or mexiletine than in those receiving placebo (35 versus 12 percent, respectively).

A consensus guideline from the Reflex Sympathetic Dystrophy Syndrome Association1 mentions mexiletine as a “somewhat experimental” option for treatment of this condition. A second consensus guideline2 similarly notes that although mexiletine is an option, it is not considered a first- or second-line medication.

Planned Early Birth vs. Expectant Management for PROM

Clinical Question

Is induction or expectant management more appropriate for premature rupture of membranes at term (PROM)?

Evidence-Based Answer

Induction of labor in patients with PROM does not increase the rates of cesarean delivery or operative vaginal delivery. Among patients who are induced there is a slightly lower incidence of chorioamnionitis (relative risk [RR] 0.74; 95% confidence interval [CI], 0.56 to 0.97) and a lower rate of infant admissions to the neonatal intensive care unit (NICU; RR 0.73; 95% CI, 0.58 to 0.91). The evidence in this study shows induction to be a reasonable option with no increased risk of operative delivery or of harm to mother or neonate.

Practice Pointers

PROM is defined as rupture of membranes that occurs at term but before the onset of labor. It occurs in approximately 8 percent of pregnancies; 50 percent of patients deliver within five hours of membrane rupture, and 95 percent of patients deliver within 28 hours.1 The most significant risk of PROM is intrauterine infection, which increases with duration of rupture. Fetal risks include cord compression and ascending infection.1 Historically, two approaches have been used: induction or expectant management. Induction involves intervening to induce labor at diagnosis or within six to eight hours of rupture of membranes. Expectant management allows the onset of labor to occur spontaneously without intervention.

Dare and colleagues performed a systematic review of randomized controlled trials to compare outcomes of induction with oxytocin (Pitocin) or prostaglandin E2 gel (Prostin E2) versus expectant management of PROM in low-risk patients. They identified 12 trials with a total of 6,814 women. Maternal mortality was examined in one study and there were no maternal deaths in either arm. There was no difference between the two management approaches in the rates of cesarean delivery or of operative vaginal deliveries. Fewer women who underwent induction developed chorioamnionitis. Compared with expectant management, one case of chorioamnionitis will be avoided for every 50 women undergoing induction for PROM. Also, there were fewer cases of endometritis in the induction groups (RR 0.30; 95% CI, 0.12 to 0.74; four trials, 445 women).

Time from rupture of membranes to birth was reduced by 13 hours in patients receiving oxytocin and by eight hours in those receiving prostaglandin compared with expectant management. Patients who underwent expectant management also had higher rates of dissatisfaction. Only one study reported uterine rupture, with one rupture in the prostaglandin arm of that study and none in the expectant management arm. This difference was not statistically significant (95% CI, 0.12 to 68.50).

There were fewer NICU admissions in the induction group. One NICU admission was avoided for every 20 women induced for PROM. In one large study, neonates born in the expectant management group were more likely to spend more than 24 hours in the NICU. However, there were no statistically significant differences between the two groups regarding infant success of breast-feeding or incidences of cord prolapse and neonatal infection.

A meta-analysis2 published in 2005 found that misoprostol (Cytotec) was as safe and effective as oxytocin for induction of patients with PROM.