Pain is the most frequent reason for emergency department visits in the United States, especially for those patients with sickle cell disease (SCD). Painful vaso-occlusive events frequently require admission to the hospital despite opioid therapy, which is the mainstay of treatment for moderate to severe pain in SCD. Achieving adequate pain control with escalating doses of opioid analgesics may be difficult due to tolerance, physical dependence, and side effects. Common side effects include pruritus, nausea and vomiting, constipation, urinary retention, sedation, and respiratory depression. With the recent focus on the opiate crisis there has been a push towards the use of alternative to opiates (ALTO) for a variety of pain syndromes.
Lidocaine is a class 1b sodium channel blocking agent that is typically used as an anti-arrhythmic and local anesthetic. This medication also has potent anti-inflammatory, anti-hyperalgesic, and gastrointestinal pro-peristaltic properties. Lidocaine may be useful as an adjunct to opioids in response to a painful sickle cell crisis. Intravenous (IV) lidocaine infusion has previously shown benefit in neuropathic pain, renal colic, and peri-operative pain. No prospective studies have evaluated lidocaine for SCD pain thus far.
A previous retrospective study evaluated lidocaine infusion as adjuvant therapy to patients with SCD. Eleven patients were given a total of 15 IV lidocaine trials. Investigators found clinical improvement in pain score from pre-lidocaine challenge to 24 hours post (defined as a \>20% reduction in pain scores) in 53.3% (8 of 15) of patients. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre to 24 hours post lidocaine was 32.2%. Two patients experienced disorientation and dizziness. The authors concluded that lidocaine was able to provide pain relief and reduce the amount of morphine necessary during SCD vaso-occlusive crisis and that prospective studies are needed to determine its true efficacy, dosing, and tolerability.
A prospective, single-arm, phase II trial evaluated lidocaine 5% patches for neuropathic pain and pain related to vaso-occlusive sickle cell crises in children ages 6 to 21 years old. Patches were applied to the painful area for 12 hours a day. The primary endpoint was the proportion of inpatients with significant pain relief defined as a decrease of at least 2 points on the visual analog pain scale (VAS, from 0-10) measured at 12 hours after patch placement over two consecutive days. The use of additional treatments such as antiepileptics and opioids were allowed and their usage was documented. The primary outcome of VAS improvement of \>2 over 2 consecutive days was observed in 48.6% of evaluated patients (19/39). Transdermal lidocaine was tolerated well with only 3 minor adverse events reported (two localized skin reactions and one generalized skin eruption) and no serious adverse events.
The theoretical benefits along with the two previously discussed studies provide evidence to further investigate the use of lidocaine in SCD pain. Studies are needed to know whether lidocaine may be able to benefit alleviate pain quicker and minimize need for opiates similarly to its use in renal colic. This prospective trial aims to evaluate whether lidocaine can decrease the opiate needs during a SCD crisis while providing adequate pain relief and tolerability.
