A pregnant patient with chronic regional pain syndrome (CRPS) and indwelling spinal cord stimulator presented with twin gestation for induction of preterm labor due to preeclampsia. Intravenous magnesium was initiated and a lumbar epidural catheter was placed uneventfully for labor analgesia. The patient reported complete relief of her CRPS-associated pain during and for 24 hours after delivery, while receiving intravenous magnesium, with her pain symptoms returning shortly after discontinuing magnesium. To our knowledge, there are no case reports that describe CRPS-associated pain relief while on peripartum magnesium therapy.
- chronic regional pain syndrome
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
Magnesium has long been used for seizure prophylaxis in preeclampsia. In addition, magnesium is known to modulate pain through inhibition of N-methyl-d-aspartate (NMDA) receptor activation,1 and its perioperative administration has been shown to enhance postoperative analgesia.2 We report the cessation of chronic regional pain syndrome (CRPS)-related pain during the treatment of preeclampsia with magnesium, and review the current evidence regarding magnesium as a possible analgesic in the treatment of CRPS-related pain. As physicians, it is our duty to always remain vigilant in seeking new ways to treat our patients, and we contend that this case will contribute to further investigation in concordance with the CARE guidelines.3
A 29-year-old, 92 kg primagrivida presented with a dichorionic-diamniotic twin pregnancy at 35 4/7 weeks gestation with increased systolic blood pressure, headaches, and visual changes. She had a history of migraine headaches, chronic back pain, and poorly controlled type 1 CRPS following a foot injury 10 years prior. She had undergone multiple extensive and comprehensive assessments by pain management consultants, as well as numerous intervention trials, including various analgesic medications, ketamine and magnesium infusions, plasmapheresis, and implantation of a spinal cord stimulator (SCS) (figure 1), all with limited success. Of note, her prior magnesium therapy was in a different state, and information as to specific dosing regimen was unavailable. When she became pregnant, she learnt from her obstetric provider that the only reported safe interventions for CRPS in pregnancy include ascorbic acid, physical therapy, and transcutaneous electrical nerve stimulation therapy. Despite case reports of safe use of SCS in pregnant women, the patient chose to have her SCS turned off, and she discontinued all other therapies.
Her blood pressure on admission was 160/94, and she endorsed a headache that felt different from her baseline migraines, and new onset blurred vision. In addition to the diagnosis of preeclampsia, the obstetric team was also concerned about the fetal size discordance (twin A—64th percentile, twin B—20th percentile), and delivery was recommended. Her platelet count was 94 000 (with a prior count of 186 000). Her headache and blood pressure improved following acetaminophen and initiation of magnesium therapy (6 g intravenous load, 2 g/hour infusion). After discussion with the obstetric team she opted for induction of labor rather than cesarean delivery.
CT scan images were available and confirmed SCS paddles at the T12-L1 level and lead wires traversing caudad to her left buttock. Risks (including abnormal or ineffective analgesia) and benefits were discussed, and the patient requested epidural analgesia at 4 cm cervical dilation. An epidural catheter was uneventfully placed at the L3-L4 interspace via a right paramedian approach, using an 18-gauge Tuohy needle with loss of resistance to saline. Complete labor analgesia and adequate sensory block (left T9-S1, right T10-L5) were achieved following administration of 2 mL 1.5% lidocaine with 5 µg/mL epinephrine (test dose) and 10 mL 0.125% bupivacaine with 5 µg/mL fentanyl. Analgesia was maintained with programmed intermittent epidural boluses (5 mL every 30 min) and patient-controlled demand doses (5 mL, lock out 10 min) using a solution of 0.1% bupivacaine with 2 µg/mL fentanyl.
Her systolic blood pressure remained well controlled between 120 and 134 mm Hg throughout labor. She progressed to complete cervical dilation 13 hours after epidural placement and was taken to the operating room for an uncomplicated vaginal twin delivery 30 min later, after which the epidural catheter was removed. Magnesium infusion was continued for 24 hours postpartum for seizure prophylaxis. Although she experienced some weakness and fatigue from hypermagnesemic therapy, she reported complete pain relief of her CRPS symptoms long after her epidural analgesic block had resolved, throughout the time she received magnesium. This was notable for being the only time in 10 years that she recalled being pain-free. Soon after discontinuation of magnesium, her CRPS symptoms returned.
In a follow-up conversation 14 months later, the patient reported that, beginning 4 months postpartum, she has undergone intravenous magnesium treatments once or twice per week, with a dose of 1 g over 2 hours. In her words, “Those are the best 2 hours of my week.” During the infusion, she experiences some fatigue, but reports that her pain is reduced from her typical 7 to 9 out of 10 severity to 5 out of 10, which she describes as tolerable. The analgesia is short-lived, though, and the 1 hour drive each way to the clinic for this treatment is not easy for this mother of 2. She states that, despite her request, her pain management specialist is reluctant to infuse larger doses of magnesium. Serum magnesium levels were never measured perioperatively, but she reports that her levels have been assessed in the past and have never demonstrated deficiency. The patient remains hopeful for better and more long-lasting pain relief in the future as she continues to pursue pain management consultation regarding other potential CRPS pain therapies.
This patient’s dramatic and complete alleviation of lower extremity CRPS pain was initially presumed to be due to her labor epidural analgesic block. However, complete analgesia continued long after discontinuation of her epidural, and temporally mirrored the continuous infusion of magnesium. Although systemic local anesthetics attenuate neuropathic pain, our patient experienced complete analgesia for over 24 hours after discontinuing low-dose epidural bupivacaine administration. Additionally, the possibility of epidural-associated sympathetic blockade must be considered given that sympathetic chain blockade is a well-known therapy for CRPS. However, this therapy had failed multiple times in the past for this patient and therefore would be a less likely explanation in this circumstance. Finally, while a synergistic effect of concurrent magnesium and local anesthetic is also theoretically possible, it is notable that her CRPS pain returned soon after discontinuation of magnesium therapy, consistent with hypermagnesemia as the primary, if not sole, mechanism underlying her CRPS-related analgesia. This conclusion is supported by evolving knowledge regarding the role of magnesium in pain signaling.
Activation of the NMDA receptor excitatory amino acids (aspartate and glutamate) is thought to be pivotal in neuronal sensitization. Magnesium ions inhibit NMDA receptor activation by producing voltage-dependent block of calcium ion influx through the receptor channel.1 In preclinical studies, systemically and intrathecally administered magnesium enhances opioid analgesia, especially in persistent neuropathic and inflammatory pain models.1 4 In humans, systemically and neuraxially administered magnesium produces modest reductions in postoperative pain and opioid requirements, especially if continued into postoperative period.1 2 5
At odds with our case, two trials of magnesium monotherapy have failed to demonstrate any therapeutic effect in patients suffering CRPS, when compared with placebo.6 7 However, both studies involved intermittent outpatient administration of magnesium—70 mg/kg intravenously over 4 hours daily for five consecutive days in one,6 and 1–2 g intramuscularly daily for 7 days intramuscularly daily in the other.7 Neither study provided details regarding analgesia experienced during or immediately after magnesium administration. The doses of magnesium used in these studies were significantly lower than that administered in preeclampsia. In our case, a 6 g loading dose (65 mg/kg) was administered rapidly followed by a 2 g/hour maintenance infusion to meet seizure prophylaxis target concentrations (3.5–7 mEq/L) for the duration of labor and for 24 hours postpartum. This significant dose difference suggests a possible dose-response effect. Additionally, it is possible that hypermagnesemia potentiated analgesic effects of residual systemic fentanyl. A similar epidural fentanyl regimen has been reported to produce mean maternal plasma concentrations of 0.17 ng/mL, regardless of duration of infusion,8 and presence of plasma fentanyl, with an elimination half-life of more than 190 min, has been shown to persist for a long time after even a single epidural dose.9
In conclusion, in contrast to negative reported results from human trials of magnesium therapy for CRPS, hypermagnesemic therapy for preeclampsia in a patient with poorly controlled CRPS was associated with complete alleviation of her chronic lower extremity pain until magnesium therapy was discontinued. Although analgesia did not persist beyond the window of acute treatment, thereby limiting immediate direct clinical application, this report adds to evolving evidence regarding magnesium’s role in the physiology of pain and its potential role in analgesia.
Presented at This report was presented in part at the 2018 annual meeting of the Society for Obstetric Anesthesia and Perinatology in Miami Beach, 9–13 May 2018.
Contributors JAN and MGR collaboratively researched, wrote, revised, and finalized this manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.