Orthopedics · Medical Literature
Effects of Combined Intravenous and Topical Magnesium Sulfate Administration on Pain, Stress, and Functional Recovery After Total Knee Arthroplasty: A Prospective, Randomized, Blinded Controlled Trial.
Abstract
Evidence suggests that both intravenous and intraoperative topical application of magnesium sulfate can improve pain management after total knee arthroplasty (TKA). However, the optimal method of magnesium sulfate administration remains unclear, and no studies have evaluated the effect of combined intravenous and topical application on post-TKA pain management. This study aimed to assess the effects of combined intravenous and topical magnesium sulfate on pain, stress, and functional recovery following TKA. In this randomized controlled trial, 150 patients undergoing TKA were randomly assigned to one of three groups: the Intravenous Group (received intravenous magnesium sulfate intraoperatively), the Topical Group (received magnesium sulfate added to the local infiltration analgesic cocktail), and the Combined Group (received both intravenous and topical magnesium sulfate). The primary outcome was the resting pain score at 24 hours postoperatively. Secondary outcomes included pain scores at other time points, postoperative morphine consumption for rescue analgesia, postoperative knee range of motion, walking ability, hospital length of stay, intraoperative stress levels (intraoperative inhaled anesthetic consumption, incidence of intraoperative hypertension), postoperative stress levels (postoperative serum cortisol/ACTH levels), and complication rates. No significant difference was found in the resting Visual Analogue Scale (VAS) pain scores at 24 hours postoperatively among the three groups. Compared to the Intravenous and Topical groups, the Combined Group showed significantly lower VAS scores at several time points on the day of surgery, although this did not reach the minimal clinically important difference. No significant differences were observed among the three groups for the other secondary outcomes. Compared with intravenous or topical magnesium sulfate alone, combined intravenous and topical administration did not demonstrate a clinically significant advantage in postoperative pain management, stress response, or functional recovery. Further studies are warranted to determine the optimal route and regimen for perioperative magnesium sulfate administration in TKA.
Clinical relevance
In patients undergoing primary unilateral total knee arthroplasty (TKA) for knee osteoarthritis, does combined intravenous plus topical (local infiltration analgesic cocktail) administration of magnesium sulfate produce superior postoperative pain control, stress response attenuation, and functional recovery compared with either route of administration alone? __SNAPSHOT__ {"studyDesign":"Prospective, randomized, blinded (partially), three-arm controlled trial","setting":"Single institution, China; consecutive patients enrolled August 2025 – February 2026; registered prospectively in the Chinese Clinical Trial Registry (ChiCTR2500107495)","sampleSize":"n = 150 (Intravenous Group: 50, Topical Group: 50, Combined Group: 50)","population":"Consecutive adult patients scheduled for primary unilateral TKA for knee osteoarthritis; specific inclusion/exclusion criteria not fully reported in the abstract","intervention":"Combined Group: intravenous magnesium sulfate administered intraoperatively PLUS magnesium sulfate added to the local infiltration analgesic (LIA) cocktail (topical/periarticular)","comparator":"Intravenous Group: intravenous magnesium sulfate alone intraoperatively; Topical Group: magnesium sulfate added to LIA cocktail alone","primaryOutcome":"Resting Visual Analogue Scale (VAS) pain score at 24 hours postoperatively","followUp":"Perioperative and early postoperative period; exact total follow-up duration not reported in the abstract","fundingSource":"Not reported"}
Key findings
For the primary outcome, no statistically significant difference was found in resting VAS pain scores at 24 hours postoperatively across the three groups. Post-hoc pairwise comparison between the Intravenous and Topical groups also showed no significant difference (p = 0.192). For dynamic (movement) pain, the Combined Group demonstrated statistically significantly lower overall movement VAS scores compared with the Intravenous Group (p = 0.035) and the Topical Group (p = 0.001); however, the authors reported that these differences did not reach the prespecified threshold for minimal clinically important difference (MCID), and therefore did not represent a clinically meaningful advantage. Absolute VAS values, effect sizes, confidence intervals, and NNT are not reported in the available abstract. No significant differences were observed among the three groups in postoperative morphine hydrochloride consumption for rescue analgesia, knee range of motion, postoperative ambulation capacity, or length of hospital stay. No significant differences were found in intraoperative or postoperative stress markers (inhaled anesthetic consumption, incidence of intraoperative hypertension, postoperative serum cortisol/ACTH levels) or in complication rates.
Practice implications
This trial established that combining intravenous and topical magnesium sulfate administration does not confer a clinically meaningful advantage over either route alone for any pre-specified outcome domain in TKA — including the primary endpoint of resting pain at 24 hours, opioid rescue requirements, functional recovery milestones, perioperative stress biomarkers, or complication rates. The statistically significant reduction in movement VAS scores observed with the Combined Group at certain early time points on the day of surgery explicitly did not meet the MCID threshold, and no significant difference between IV-only and topical-only arms was observed, leaving the question of route superiority unresolved. This is, to the authors' knowledge, the first RCT directly comparing all three strategies. Findings apply to adult patients undergoing primary unilateral TKA for knee osteoarthritis at a single Chinese center; generalizability to revision arthroplasty, bilateral procedures, Western populations, or settings using substantially different multimodal analgesia backgrounds (e.g., adductor canal blocks, liposomal bupivacaine) is not established. Patients with significant comorbidities, renal impairment, or those receiving concurrent neuraxial or peripheral nerve block analgesia were likely not fully represented. Specific magnesium dosing regimens were not detailed in the abstract. Results do not support adding a second route of magnesium sulfate administration to an established single-route protocol. Only the abstract was available for review; full-text data, including raw group means, confidence intervals, and power calculations, could not be verified independently — this should be considered a limitation of this summary. __LIMITATIONS__ Single-center design with a predominantly Chinese patient population limits external generalizability.,Sample size of 50 patients per arm is modest; the study may have been powered for the primary VAS endpoint but likely underpowered to detect differences in secondary functional and stress outcomes.,Blinding method described as 'blinded' but not confirmed as double-blind for all parties (patient, surgeon, assessor, analyst); specific blinding procedures are not detailed in the abstract.,The abstract does not describe the specific magnesium sulfate doses used in each arm, which limits clinical replication.,No placebo/saline control arm was included; the trial compares active regimens only, so the absolute analgesic contribution of magnesium sulfate versus background multimodal analgesia cannot be isolated.,Short and incompletely specified follow-up period; longer-term outcomes (persistent postsurgical pain, patient-reported outcomes beyond discharge) are not reported.,Stress response surrogates (cortisol, ACTH, anesthetic consumption, intraoperative hypertension incidence) are physiological proxies; their clinical significance as independent outcomes in this context is unclear.,Funding source is not reported, limiting assessment of potential conflicts of interest.,Consecutive enrollment from a single institution introduces potential selection bias.,Only the abstract was available for this summary; full-text verification of statistical methods, randomization sequence, allocation concealment, and per-protocol vs. intention-to-treat analysis was not possible. __BOTTOM_LINE_CATEGORY__ low_certainty __BOTTOM_LINE__ In this 150-patient, three-arm RCT, combined intravenous plus topical magnesium sulfate did not demonstrate a clinically meaningful advantage over either route alone across any primary or secondary outcome — including resting pain at 24 hours, opioid consumption, functional recovery, perioperative stress, or complications — in patients undergoing primary TKA. Clinicians should not routinely combine both delivery routes of magnesium sulfate based on these findings. Further multicenter RCTs incorporating a placebo control arm, standardized dosing, and longer follow-up are needed before any definitive recommendations on optimal magnesium sulfate administration strategy in TKA can be made.