This editorial from Anesthesia & Analgesia highlights many influential articles regarding the effective use of magnesium in the intraperative setting.

Takeaway

Due to its antinociceptive and antispasmodic pharmacologic effects, wide therapeutic window, as well as potential positive impact on acute and chronic pain, magnesium is an underrepresented non-opioid adjuvant for perioperative pain management. Magnesium could serve as an effective intervention to improve postoperative pain outcomes and reduce both analgesic and anesthetic requirements in surgical patients.

Excerpts

magnesium has been shown to potentiate antinociceptive properties of other drugs, such as ketamine, and also provide opioid-sparing benefits

perioperative magnesium reduces anesthetic requirements (particularly during induction and maintenance), limits use of nondepolarizing neuromuscular blocking agents, and reduces intraoperative opioid use.

opioid-sparing effect and a reduction in postoperative pain after sleeve gastrectomy and total abdominal hysterectomy

In studies evaluating catheter related bladder discomfort after transurethral resection of bladder tumor (TURBT), intravenous magnesium provided antispasmodic effects in the immediate postoperative period

potential contribution to the prevention of chronic postsurgical pain via its mechanism of inhibiting central sensitization

Physiology Refresher on Mangesium Sulfate

NMDA Receptor Activity

In the nondepolarized state, magnesium acts as a natural NMDA receptor antagonist, blocking sodium and calcium influx. During depolarization, magnesium is displaced, allowing for signal propagation. In pain states, prolonged depolarization leads the release of excitatory neurotransmitters, such as glutamate and substance P, enhancing pain signaling and causing central sensitization. Increasing magnesium levels can dampen the signal signal cascade.

Magnesium works both peripherally and centrally to reduce pain. In the spinal cord, it lowers dorsal horn excitability, reducing pain transmission. Peripherally, it stabilizes nerve membranes, decreasing excitability and maintainig pain thresholds.

NMDA receptors are also involved in opioid tolerance. Blocking these receptors can enhance analgesia and may reduce opioid use.

Reduction of Calcium-Mediated Excitation:

Calcium is critical for neurotransmitter release at synaptic junctions. Presynaptic calcium channel drive acetylcholine release at neuromuscular junctions. Magnesium competes with calcium at these sites, relaxing smooth muscle by inhibiting myosin light chain kinase in the vasculature, airway, and uterus. This reduces pain linked to muscle spasms.

Anti-inflammatory Properties

Magnesium sulfate also has anti-inflammatory effects, through molecular pathways that drive inflammation. It lowers cytokine production and release by modulating intracellular calcium levels. Inflammation causes oxidative stress and generates reactive oxygen species (ROS), damaging cellular components and amplifying the inflammatory response. Magnesium reduces ROS, limits tissue irritation and and nociceptive stimulation, and thus decreases pain.

🩺 Clinical Pearls for Anesthesia Providers:

• Dosing: bolus dose (30–50 mg/kg) followed by a continuous infusion (6–20 mg/kg/h)
• Patient Selection: Especially beneficial in patients at risk for chronic pain, high opioid consumption, or opioid-related complications.
• Safety Profile: Generally well-tolerated, but attentive care is needed in patients with renal impairment or hypotension.

Citation

Kwater, A. , Grant, M. & Gan, T. (2025). Magnesium and Its Emerging Role in Perioperative Pain Management. Anesthesia & Analgesia, 140 (1), 51-53. doi: 10.1213/ANE.0000000000007121.

Editorial Link