Guest Skeptic: Dr. Sergey Motov is an Emergency Physician in the Department of Emergency Medicine, Maimonides Medical Center in New York City. He is also one of the world’s leading researchers on pain management in the emergency department.
Case: A 37-year-old man presents to the emergency department (ED) with severe right-sided flank pain. The pain started about eight hours ago as a vague discomfort in his right flank, but it has gotten progressively worse and now is radiating to his groin. Patient reports nausea, an increased urge to urinate and noticing blood in his urine on one occasion. The patient denies prior medical or surgical history.
Upon ED arrival, his vital signs are normal. Physical examination revealed a stated age patient in distress due to severe right flank pain, prominent right-sided costovertebral angle tenderness, and absence of abdominal tenderness or guarding. While strongly considering renal colic in differential diagnosis and reaching for the bedside ultrasound, you are wondering if a single dose of a non-steroidal anti-inflammatory (NSAID) will be enough to relieve this patient’s pain, or should you add Magnesium or Lidocaine?
Background: Renal colic is a common and extremely painful emergency department (ED) complaint encountered in the ED that frequently recurs. The nonsteroidal anti-inflammatory drugs (NSAIDs) given intravenously or intramuscularly (IM) are frequently used as first-line therapy. However, about 30% of ED patients receiving NSAIDS require rescue analgesia in the form of opioids. Opioid use, though effective, is limited at times due to the potentially dangerous adverse effects. Thus, there might be a role for other non-opioid classes of drugs to be co-administered with NSAIDs for relief of renal colic.
Magnesium sulfate (MgSO₄) has been suggested as a possible treatment option. It may blunt ureteral smooth muscle spasm by antagonizing calcium influx in smooth muscle and by N‑methyl‑D‑aspartate (NMDA) receptor antagonism. These are mechanisms that can reduce visceral pain and augment other analgesics. Small ED trials and meta‑analyses suggest MgSO₄ can reduce pain scores and opioid use in renal colic, though the evidence base has been limited and heterogeneous [1].
Another suggested treatment modality for renal colic is intravenous lidocaine. We looked at this treatment on SGEM#202 and were unimpressed with the efficacy. Systemic lidocaine blocks voltage‑gated sodium channels and appears to modulate central sensitization and visceral pain pathways. In ED populations, systematic reviews indicate IV lidocaine offers variable analgesia with a mixed signal for benefit, and renal colic–specific RCTs suggest it may be inferior to ketorolac and best considered (if at all) as part of a multimodal strategy rather than as monotherapy [2].
Clinical Question: In adult ED patients with suspected renal colic receiving IM diclofenac, does adding IV magnesium sulfate or IV lidocaine increase the proportion achieving ≥50% reduction in pain at 30 minutes compared to a saline placebo?
Reference: Toumia M, Sassi S, Dhaoui R, et al. Magnesium Sulfate Versus Lidocaine as an Adjunct for Renal Colic in the Emergency Department: A Randomized, Double-Blind Controlled Trial. Ann Emerg Med 2024
Authors’ Conclusions: “Adding intravenous MgSO4, but not lidocaine, to IM diclofenac offered superior pain relief but at levels below accepted thresholds for clinical importance.”
Quality Checklist for Randomized Clinical Trials:
Results: They screened 1,321 patients and included 840 who were randomized (280 per arm). The mean age is in the mid 40s with a fairly even male/female split. The mean baseline NRS ~8.5–8.7. Ultrasound showed stones in ~20% and pyelocaliceal dilation in over one-third of patients.
Key Result: Adding IV MgSO₄ to IM diclofenac increased the proportion of patients achieving ≥50% pain reduction at 30 min and reduced rescue analgesia use, but pain score differences never reached the 1.3‑point MCID, while IV lidocaine was not superior to diclofenac alone.
Primary Outcome: ≥50% NRS reduction at 30 minutesMgSO₄ + diclofenac: 227/280 (81.7%)Lidocaine + diclofenac: 204/280 (72.9%)Placebo + diclofenac: 201/280 (71.8%)MgSO₄ vs lidocaine +8.8% (95% CI 1.89–15.7, p=0.013)MgSO₄ vs control +9.9% (95% CI 2.95–16.84, p=0.004).Secondary Outcomes:Rescue analgesia: Lower need in MgSO₄ group (17.1%) versus lidocaine (22.5%) and control (28.9%).Time to 50% pain reduction: No significant differences between groups (approximately 21 minutes for all groups).Persistent pain at 90 minutes: Similar across groups (20-22.1% with NRS>2).Return ED visits: No differences (22-26%)Adverse events: Significantly more in MgSO₄ group (57.1%) versus control (22.5%), primarily facial flushing (48% MgSO₄ vs 10% Lido vs 14% placebo)Statistical vs. Clinical Significance: This study exemplifies a critical issue in clinical research: achieving statistical significance without clinical importance. While the primary outcome showed statistical significance for MgSO₄ lidocaine and even more so for control, the actual NRS differences were all below 0.5 points at every time point. In addition, no between-group differences reached the generally accepted reduction of 1.3 for being clinically important [3,4]. There are concerns in the literature about what is considered a minimally important difference (MID) or minimally clinically important difference (MCID) [5, 6].Choice of Primary Outcome Metric: The primary outcome was the proportion of patients achieving ≥50% pain reduction rather than the actual change in pain scores. This dichotomization of a continuous variable has several problems:Loss of Information: Converting continuous NRS data to a binary outcome discards valuable information about the magnitude of pain relief. For example, a patient going from NRS 10 to 5 (50% reduction) is counted the same as a patient going from 10 to 2 (80% reduction), yet these represent vastly different clinical scenarios.Arbitrary Threshold: The 50% reduction threshold, while commonly used, may not represent meaningful relief for all patients. For example, some patients with NRS 10→5 may still require rescue analgesia, while others with NRS 10→6 (40% reduction) might be satisfied.Diagnostic Verification of Kidney Stone: The diagnosis of renal colic was based on emergency physician clinical judgment or imaging with ultrasound showing direct or indirect signs of urinary tract stones in only 58% of participants when performed. This is consistent with current radiology, emergency medicine and urology guidelines not to get imaging on all patients [7]. We cover this on the SGEM Xtra: Come Together, Right Now…Over Renal Colic. While this approach may increase real-world applicability (generalizability), the “suspected renal colic” inclusion without universal confirmatory imaging may reduce internal validity and introduce misclassification bias. A confirmed stone sensitivity analysis would have helped strengthen the findings.Adjunct to IM Rather Than IV NSAID: While acknowledging and respecting the authors’ standard of care practice of using IM Diclofenac, there are several important implications:Delayed NSAID Absorption: IM administration results in slower and more variable absorption compared to IV administration. Peak plasma concentrations occur at 20-60 minutes with IM NSAIDs versus 5-10 minutes with IV administration. This delay may have limited the synergistic potential of the IV adjuncts.Limited generalizability: The authors stated that IM diclofenac is “most frequently administered in our emergency setting,” which may reflect local practice but limits generalizability to settings using IV NSAIDs more globally, with IV ketorolac being the most used NSAID.Timing of Effect: The NRS measurements at 5, 10, and 20 minutes may primarily reflect the IV medication effects, while the 30 to 90-minute assessments may include increasing contribution from the IM diclofenac. This could confound the interpretation of the adjunct effects.Multiple Injections: Patients received both an IM injection and IV access/infusion, increasing procedural burden (and unnecessary pain) compared to a single IV administration strategyUnmasking: Both agents were given as single boluses over 2-4 minutes rather than short infusion (a common practice in North America when used for pain) that might have been responsible for much higher rates of “minor” adverse effects (facial flushing and vomiting) in the Magnesium Group, and dizziness in the Lidocaine group. These adverse events may have unmasked the patient and clinicians to group allocation. To investigate this potential bias, it would have been helpful to survey the participants and clinicians as to which group they thought the patient had been randomized to.Comment on Authors’ Conclusion Compared to SGEM Conclusion: We would have tweaked the conclusion to say: Adding intravenous MgSO₄, but not lidocaine, to IM diclofenac MAY offer superior pain relief, but at levels below accepted thresholds for clinical importance.
SGEM Bottom Line: While MgSO₄ when added to IM NSAIDs for renal colic, may provide a statistically superior pain relief to Lidocaine and Placebo, and less rescue opioid use, the magnitude of benefit is small, has questionable clinical relevance and comes with an increased rate of adverse effects.
Case Resolution: You proceeded with administration of 10mg of IV Ketorolac as a single agent, and upon assessment of the patient at 20 minutes, the patient verbalized significant pain relief without experiencing any adverse effects. Urinalysis is positive for blood, while complete blood count, complete metabolic panel, and the remainder of the urinalysis are normal. A non-contrast CT scan reveals a 4 mm non-obstructing stone in the right distal ureter.
Clinical Application: Intravenous adjunctive MgSO₄ does not seem to provide clinically meaningful pain relief in patients with renal colic but leads to frequent development of facial flashing. This precludes if from routine use in the ED for patients with renal colic. Similarly, IV lidocaine combined with parenteral NSAIDs does not provide clinically meaningful pain relief in patients with renal colic, and the evidence doesn’t support its use at this time.
What Do I Tell the Patient? It looks like you have classic kidney‑stone pain. I will order an IV analgesic called ketorolac that should reduce your pain and make you more comfortable. However, if you are still in pain in 15-20 minutes after receiving this medication, I will proceed with ordering intravenous morphine.
Keener Kontest: Last week’s winner was Dr. Steven Steltz from NZ. He knew it was called Cable Beach in Broome, Western Australia, because it was the site where an undersea telegraph cable came ashore in 1889, connecting Australia to the rest of the world via Java.
Listen to the SGEM podcast this week to hear the trivia question. If you know the answer, send an email to [email protected] with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.
Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.
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