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PACULit Newsletter - March 3 2025

High-Impact Studies Review — March 2025

Stay updated with the latest breakthrough research in emergency medicine, critical care, and advanced therapeutics.

Featured Educational Video

This month's featured educational video provides an in-depth discussion on emerging treatments in emergency medicine and critical care. Our medical experts review the key research findings presented in this newsletter, with practical applications for your clinical practice.

1. Magnesium Sulfate vs. Lidocaine as an Adjunct for Renal Colic
Annals of Emergency Medicine | December 2024

This randomized, double-blind controlled trial compared the effectiveness of intravenous MgSO4 and lidocaine as adjuncts to diclofenac for managing acute renal colic in the emergency department setting.

Patients Achieving ≥50% Pain Reduction at 30 Minutes
81.7%
MgSO4
72.9%
Lidocaine
71.8%
Control
Statistically significant differences: MgSO4 vs. Lidocaine (p=0.013) and MgSO4 vs. Control (p=0.004)
Key Findings:
  • MgSO4 showed statistically superior pain relief compared to lidocaine and placebo
  • The magnitude of differences was below the accepted threshold for clinical importance
  • MgSO4 group required less rescue analgesia
  • More adverse events in the MgSO4 group, primarily facial flushing (48.2%)
Clinical Implications:
  • Use MgSO4 cautiously, balancing marginal benefits with adverse event risks
  • Lidocaine showed no major benefit over diclofenac alone
Clinical Pharmacist's Perspective

The modest analgesic benefit of IV magnesium must be weighed against the high incidence of facial flushing (48.2%). When administering IV MgSO4, ensure patients are warned about this common side effect to prevent unnecessary anxiety. From a cost perspective, MgSO4 is an inexpensive adjunct that may reduce the need for opioid rescue medication. Consider it in patients with contraindications to opioids or those with prior inadequate response to NSAIDs alone. The 1g dose used in this study is well below the threshold for serious toxicity, making it relatively safe even in patients with mild renal impairment.

Full Article
2. Intranasal Ketamine as an Adjunct to Fentanyl for Prehospital Trauma Pain
Annals of Emergency Medicine | October 2024 (Epub January 12, 2024)

This randomized, placebo-controlled trial evaluated whether adding intranasal ketamine to fentanyl improves early pain control after traumatic injury in the out-of-hospital setting.

Patients Achieving ≥2-Point Pain Reduction at 30 Minutes
44.7%
Ketamine
36.0%
Placebo
Difference not statistically significant (8.7%, 95% CI [5.1% to 22.5%], P=0.22)
Key Findings:
  • No statistically significant difference in pain reduction between ketamine (44.7%) and placebo (36.0%)
  • The observed difference of 8.7% suggests a trend that might warrant further investigation
  • No differences in pain scores at any time point through 3 hours
  • No difference in need for additional pain medications
  • Side effects were similar between groups with no concerning safety signals
Clinical Implications:
  • A single 50 mg intranasal dose of ketamine appears safe but current evidence doesn't support a significant analgesic benefit
  • Higher doses might be worth exploring in future studies
Clinical Pharmacist's Perspective

The bioavailability of intranasal ketamine is approximately 40%, meaning the 50mg dose used in this study translates to roughly 20mg of systemic exposure. This is likely at the lower end of effective analgesic dosing for adults. While the observed 8.7% improvement didn't reach statistical significance, this trend suggests that higher doses might be more effective. For EMS protocols, intranasal administration remains attractive for its ease of use and avoidance of vascular access, but based on this study, higher intranasal doses (75-100mg) may be worth investigating. Remember that absorption of intranasal medications can be compromised by nasal congestion, bleeding, or prior intranasal medication administration, which may have affected the results here.

Full Article
3. Transfusion Practices in Traumatic Brain Injury (TBI): A Systematic Review & Meta-Analysis
Critical Care Medicine | February 2025

This comprehensive review examined whether liberal blood transfusion strategies improve neurologic outcomes in TBI patients compared to restrictive strategies across five randomized controlled trials involving 1,533 patients.

Neurologic Outcomes (Favorable Glasgow Outcome Scale)
1.16
Liberal
1.00
Restrictive
Risk Ratio: 1.16 (95% CI 1.00-1.34)
Acute Respiratory Distress Syndrome (ARDS) Risk
1.78
Liberal
1.00
Restrictive
Risk Ratio: 1.78 (95% CI 1.06-2.98)
Key Findings:
  • Trend toward better neurologic outcomes with liberal transfusion that approaches statistical significance (RR, 1.16; 95% CI, 1.00-1.34)
  • No significant differences in mortality rates between groups at any time point
  • Liberal strategy was associated with significantly higher prevalence of ARDS (RR, 1.78; 95% CI, 1.06-2.98)
  • Liberal strategy group received significantly more blood units per patient
Clinical Implications:
  • Current guidelines recommending restrictive transfusion protocols (Hb < 7 g/dL) should be reconsidered for TBI patients
  • The 9 g/dL threshold may represent an optimal balance between brain oxygenation and transfusion risks
  • Despite increased ARDS risk, the potential neurologic benefits should be considered when making transfusion decisions
  • Future research should explore the ideal hemoglobin threshold specifically for TBI patients
Clinical Pharmacist's Perspective

While pharmacists don't directly administer blood products, understanding transfusion thresholds is essential for comprehensive patient care in critical care settings. This meta-analysis suggests a potential paradigm shift for TBI patients that differs from general critical care guidelines. As part of the multidisciplinary team, pharmacists should be aware that TBI patients may benefit from higher hemoglobin targets due to the brain's high oxygen demands and vulnerability to hypoxic injury. When managing patients receiving liberal transfusion strategies, be vigilant for signs of ARDS and consider how medication therapies might interact with fluid status and oxygen delivery. Pharmacists can play a role in ensuring appropriate venous thromboembolism prophylaxis is prescribed alongside transfusion strategies, as both hypercoagulable and bleeding risk considerations must be balanced in TBI care.

Full Article
🔎 Final Takeaways:
  • Magnesium Sulfate for Renal Colic: Provides statistically significant but clinically modest improvement in pain when added to diclofenac. Consider in patients who need enhanced analgesia, but be mindful of facial flushing as a common side effect.
  • Intranasal Ketamine for Trauma Pain: The addition of 50 mg intranasal ketamine to fentanyl showed a trend toward improved pain control (8.7% difference) that didn't reach statistical significance. Further research with larger sample sizes or higher doses may be warranted.
  • Liberal Transfusion in TBI: Evidence suggests that maintaining hemoglobin levels ≥9 g/dL may improve neurologic outcomes in TBI patients, but also increases ARDS risk. This challenges the standard restrictive approach and warrants further investigation.
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