The Hallway Consult — Issue #21: Minocycline for Acute Ischemic Stroke, CT Contrast and Nephrotoxicity, and Blood Pressure Targets in Acute SCI

EMPHASIS: Minocycline After Acute Ischemic Stroke Shows Real Signal

Neuroprotection in stroke has been a graveyard of good ideas. Dozens of agents that looked promising in animal models have failed when tested in humans — often because the biology doesn't translate, the treatment window is wrong, or the trials were underpowered. That's what makes EMPHASIS worth attention.

EMPHASIS enrolled 1,724 patients across 58 centers in China with acute ischemic stroke confirmed on imaging and treated them within 72 hours of symptom onset. Patients were randomized to minocycline — a 200 mg loading dose followed by 100 mg every 12 hours for 4 days — or placebo. The primary outcome was excellent functional recovery, defined as a modified Rankin Scale score of 0 or 1 at 90 days.

The result was positive: 52.6% of patients in the minocycline group achieved mRS 0–1 at 90 days compared with 47.4% in the placebo group. The absolute difference translates to a number needed to treat in the range that gets attention in stroke circles. The mechanism is thought to involve minocycline's anti-inflammatory and neuroprotective properties — it crosses the blood-brain barrier, inhibits microglial activation, and reduces ischemia-related apoptosis. Safety profile was consistent with the known minocycline profile; serious adverse events were similar between groups (4.6% vs 5.9%).

This is not a paper that changes U.S. practice today. The trial was conducted in China, the study population may differ from Western stroke populations in ways that affect generalizability, and minocycline is not an approved stroke treatment anywhere. Independent replication is needed before clinical uptake. But EMPHASIS is a genuinely positive stroke neuroprotection trial in a field that has had almost none, and it was double-blind, randomized, and adequately powered. That is noteworthy.

For EM clinicians, the practical implication right now is awareness: this agent is likely to appear in trials, conversations, and consultant discussions. Minocycline is cheap, widely available, and has a favorable safety record from its decades of use for skin infections and rheumatologic conditions. Whether it earns a formal role in acute ischemic stroke management will depend on replication and guideline uptake — but the EMPHASIS result is not something to wave off.

Bottom line: EMPHASIS, a double-blind RCT of 1,724 patients across 58 centers, found that minocycline (200 mg loading dose, then 100 mg every 12 hours for 4 days) improved excellent functional outcomes at 90 days compared with placebo in acute ischemic stroke. This is a legitimate positive signal in a historically barren field, though the study was conducted in China and practice change awaits independent replication.

Lu Y, Guan L, Wu J, Yang Q, Zhang M, et al. Efficacy and safety of minocycline in patients with acute ischaemic stroke (EMPHASIS): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2026;407(10529):679-688.

CT Contrast and Nephrotoxicity: The Dose Is Below the Threshold

The fear of contrast-induced nephropathy has shaped emergency medicine practice for decades. Generations of EM physicians have watched CTs get delayed, downgraded, or withheld while nephrology got called or creatinine trended — even when the clinical question genuinely needed a contrast study to answer. The problem is that the evidence base for this fear has been deteriorating for years, and a new toxicological analysis makes the case more plainly than anything before it.

This paper from JEM Reports applies a dose-threshold toxicological framework — the same methodology used to evaluate drug and chemical safety — to the iodinated contrast question. The argument is straightforward: published nephrotoxicity data for iodinated contrast agents identifies a toxicological threshold of concern at approximately 120 mL. A standard clinical CT uses roughly 60–120 mL of iodinated contrast — putting routine CT doses at or below the identified threshold, and supporting the conclusion that clinically used contrast volumes fall below the level of nephrotoxic concern. Importantly, the analysis distinguishes CT doses from higher-volume procedures such as percutaneous coronary intervention, where contrast doses may approach or exceed the threshold.

This is not a retrospective cohort study trying to match contrast and non-contrast patients. It is a mechanistic, toxicological-framework argument, which means it doesn't settle every question about individual patient variation, pre-existing renal disease, or rare idiosyncratic responses. But it does crystallize the scientific argument for what observational studies have been suggesting for over a decade: contrast-induced nephropathy as a clinically meaningful phenomenon at routine imaging doses appears to be largely a myth.

For EM practice, the implication is direct. Withholding or delaying a clinically indicated contrast CT because of creatinine anxiety — in a patient who genuinely needs the study — is hard to defend. The relevant question is whether the CT is indicated, not whether the creatinine is 1.4. Policies that require nephrology clearance before contrast CTs in stable patients are not supported by the evidence.

Bottom line: A toxicological-threshold analysis concludes that the doses of iodinated contrast used in routine CT imaging fall at or below the threshold of concern for direct renal tubular toxicity, while higher-volume procedures like PCI may reach that threshold. This reinforces growing evidence that contrast-induced nephropathy at standard CT contrast doses is not a clinically meaningful risk in most patients, and supports ordering indicated contrast CTs without reflexive kidney function hand-wringing.

Phillips A, Blumenberg A. The dose of iodinated contrast required for a CT scan is below the toxicological threshold of concern for nephrotoxicity. JEM Rep. 2026 Jun;5(2).

Blood Pressure Targets in Acute SCI: The First RCT Undercuts a Long-Standing Guideline

For roughly three decades, guidelines have recommended maintaining mean arterial pressure between 85 and 90 mmHg for the first 5 to 7 days after acute spinal cord injury. The rationale is physiologically sensible: the injured cord depends on perfusion pressure to salvage ischemic but viable tissue in the injury penumbra. The problem is that this recommendation was always based on observational data and pathophysiological reasoning, not a randomized trial. Until now.

This multicenter RCT — conducted across 13 large U.S. trauma centers — randomized 92 patients with acute SCI to a target MAP of 85–90 mmHg or a standard MAP of 65–70 mmHg in the acute period. The primary outcome was change in AIS (ASIA Impairment Scale) motor and sensory scores at 6 months. The result: no significant difference in neurologic outcomes between the two groups. The higher MAP target group did not show improved motor or sensory recovery compared with the standard target group.

What the higher MAP group did show was substantially more respiratory adverse events. The vasopressor doses required to sustain MAP 85–90 pushed patients into territory where cardiorespiratory complications accumulated: respiratory complications occurred in 78% of the augmented MAP group versus 39% in the standard group (P<.001), including higher rates of pneumonia (45% vs 25%) and pulmonary edema (22% vs 7%), as well as longer mechanical ventilation.

The trial enrolled only 92 patients across two years and was stopped early due to slow enrollment — largely COVID-related — which limits definitive conclusions. The authors did not conclude that the higher MAP target should be abandoned outright, and the result should be interpreted with appropriate caution given the sample size. But this is the first RCT in this space, and the absence of neurologic benefit with the addition of significant respiratory harm is exactly the kind of signal that should accelerate guideline re-evaluation.

For EM clinicians, this lands in the "know the uncertainty" category. When a fresh SCI comes through the door and the trauma and neurosurgery teams are asking about vasopressor targets, the honest answer is now that the RCT data does not support the higher MAP target — and comes with added harm. That's a harder sell for the benefit than it used to be.

Bottom line: The first RCT of blood pressure targets in acute SCI — 92 patients across 13 U.S. trauma centers — found no neurologic benefit to maintaining MAP 85–90 mmHg versus a standard 65–70 target at 6 months, with substantially more respiratory complications in the higher-target group. The trial was small and stopped early, but this is real evidence that challenges a decades-old guideline built on observational data.

Sajdeya R, Yanez ND, Kampp M, et al. Early Blood Pressure Targets in Acute Spinal Cord Injury: A Randomized Clinical Trial. JAMA Netw Open. 2025.

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— The Hallway Consult team