Episode Title: Nausea and Vomiting in the ED: A 2025 Network Meta-Analysis of What Works Best

Episode Summary: In this Lit Hit, we break down the 2025 systematic review and Bayesian network meta-analysis by deSouza et al. regarding pharmacologic therapies for nausea and emesis. We highlight the key evidence emergency clinicians need for rapid, informed decision-making, specifically looking at which agents prevent the need for rescue medications versus those that offer the best safety profiles. This short episode delivers high-yield takeaways you can apply on your next shift to balance efficacy with side effects.

What You’ll Learn

• Top Performers for Efficacy: If the goal is avoiding the need for a rescue drug, IV tropisetron and IV prochlorperazine (Compazine) are "definitely among the most effective" agents. IV tropisetron showed a 93.9% probability of being superior, though it is currently unavailable in the United States and Canada.
• The Problem with Oral Ondansetron: While widely prescribed, oral ondansetron was found to be "definitely among the least effective" single agents for preventing the need for rescue medication.
• The Safety vs. Efficacy Trade-Off: IV ondansetron is the safety winner. It is "most likely superior" for avoiding significant adverse reactions (sedation, akathisia, dystonia). In contrast, the agents with higher efficacy potential—IV metoclopramide (Reglan), IV promethazine (Phenergan), and IV droperidol—are "definitely among the most harmful" regarding these specific adverse effects.
• Droperidol's Role: In this specific analysis of undifferentiated nausea, IV droperidol was effective (reducing the need for rescue drugs) but carried a higher risk of adverse events (OR 3.70 vs placebo). Note that this study did not identify any life-threatening arrhythmias associated with droperidol.
• Metoclopramide's Standing: IV metoclopramide falls into the "possibly among the most effective" category for efficacy but is "definitely among the most harmful" regarding adverse reactions like akathisia.

Key Clinical Tip: Context matters. This study focused on undifferentiated nausea and excluded patients with gastroparesis or Cannabinoid Hyperemesis Syndrome (CHS). The authors note that for CHS and diabetic gastroparesis, droperidol is likely the superior choice over ondansetron or metoclopramide due to different pathophysiologic mechanisms, despite the side effect risks noted in the general population.

Primary Reference: deSouza, I. S., Allen, R., Shrestha, P., Thode, H. Jr., Koos, J., & Singer, A. (2025). Efficacy and Safety of Pharmacologic Therapies for Nausea and Emesis in the Emergency Department: A Systematic Review and Bayesian Network Meta-analysis. Annals of Emergency Medicine, 86, 646-658.

Additional Resources

• Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol Use Disorder and Cannabinoid Hyperemesis Syndrome Management.

Episode Title: Major Bleeding in the ED: A 2025 Practical Guide for Optimal Management

Episode Summary: In this Lit Hit, we break down the comprehensive 2025 review "Major Bleeding in the Emergency Department: A Practical Guide for Optimal Management" and highlight the key evidence emergency clinicians need for rapid, informed decision-making. This short episode delivers high-yield takeaways regarding risk stratification, the "lethal diamond," and specific resuscitation goals that you can apply on your next shift.

What You’ll Learn

• The "Lethal Diamond" replaces the "Lethal Triad": The classic triad of coagulopathy, acidosis, and hypothermia has been updated to include hypocalcemia. Calcium is essential for the coagulation cascade; clinicians should treat hypocalcemia aggressively (ionized calcium < 1.2 mmol/L) using calcium chloride (0.5–1.0 g per 500 mL of transfused blood) to prevent dysrhythmias and coagulation defects.
• Restrictive Fluid Resuscitation is Key: For initial stabilization, use balanced crystalloids rather than saline to avoid hyperchloremic acidosis, and limit volume to a maximum of 1–2 liters. Excessive fluid administration is associated with coagulopathy, organ failure, and increased mortality.
• Targeted Blood Pressure Goals:
• • General/Trauma: Aim for "permissive hypotension" with a systolic blood pressure (SBP) target of 80–90 mmHg until bleeding is controlled.
  • Traumatic Brain Injury (TBI): If GCS < 8, maintain Mean Arterial Pressure (MAP) > 80 mmHg to ensure perfusion.
  • Intracranial Hemorrhage (ICH): Target a SBP of 130–140 mmHg to prevent hematoma expansion.
• Massive Transfusion Ratios: While defined strictly for trauma, massive transfusion protocols (MTP) are recommended for all life-threatening bleeding to prevent delays. Evidence supports a ratio of 1:1:1 or 1:1:2 (plasma:platelets:RBCs).
• Tranexamic Acid (TXA) Indications:
• • Indicated: Trauma (within 3 hours), postpartum hemorrhage, and massive hemoptysis.
  • Not Indicated: Gastrointestinal (GI) bleeding. The HALT-IT study showed no mortality benefit and an increased risk of venous thromboembolism in severe GI bleeding.
• Anticoagulation Reversal Strategy:
• • DOACs: Use specific antidotes if available (Idarucizumab for dabigatran; Andexanet alfa for Xa inhibitors). If unavailable, use 4-factor Prothrombin Complex Concentrate (PCC) at 25–50 IU/kg.
  • Warfarin: PCC is preferred over Fresh Frozen Plasma (FFP) because it reverses INR faster, has lower volume, and avoids ABO cross-matching delays. Administer with Vitamin K.
• Risk Stratification with Shock Index (SI): Because hypotension may not appear until 30% of blood volume is lost, use the Shock Index (HR/SBP). An SI > 0.91 predicts the need for massive transfusion and increased mortality in trauma.

Key Clinical Tip: When managing cirrhotic patients with variceal bleeding, avoid FFP for coagulopathy reversal if possible. FFP adds significant volume, which can increase portal pressure and worsen bleeding. Instead, favor viscoelastic test (VET)-guided use of fibrinogen concentrate or PCC.

Primary Reference: Bezati, S.; Ventoulis, I.; Verras, C.; Boultadakis, A.; Bistola, V.; Sbyrakis, N.; Fraidakis, O.; Papadamou, G.; Fyntanidou, B.; Parissis, J.; et al. Major Bleeding in the Emergency Department: A Practical Guide for Optimal Management. J. Clin. Med. 2025, 14, 784.

Additional Resources:

• European Guideline on Management of Major Bleeding and Coagulopathy Following Trauma (2023)
• British Society of Gastroenterology Guidelines for Upper/Lower GI Bleeding
• International Society on Thrombosis and Haemostasis (ISTH) Guidelines

In this Lit Hit, we break down the emerging evidence on blood-based biomarkers for mild traumatic brain injury, focusing on GFAP and UCH-L1 and their role in emergency department decision-making. We highlight what these tests can (and can’t) do, how they perform compared with CT imaging, and where they may fit alongside existing clinical decision rules. This short episode delivers high-yield takeaways you can apply on your next shift when evaluating head-injured patients.

• Which biomarkers matter most right now:GFAP and UCH-L1 are the most clinically validated blood biomarkers for mTBI, with GFAP consistently outperforming others for detecting intracranial injury.

• What they’re good at:These biomarkers have high sensitivity and negative predictive value, making them most useful as rule-out tools for clinically significant intracranial injury.

• What they’re not good at:
  Specificity is modest—positive tests do not reliably confirm intracranial hemorrhage and should not replace CT.

• Timing matters:
  Biomarker levels rise early after injury (often within 1–6 hours) and are most useful within the first 12–24 hours.

• How this fits into ED workflow:Blood biomarkers may help reduce unnecessary CT scans in low-risk mTBI when used in conjunction with clinical decision rules (e.g., Canadian CT Head Rule), not as standalone tests.

• Key controversy / clinical tip:The major debate is whether these tests meaningfully change management beyond good clinical decision rules—use them as an adjunct, not a replacement, and be cautious in elderly patients, polytrauma, or those with extracranial injuries.

Primary reference: Blood-based biomarkers for mild traumatic brain injury (GFAP, UCH-L1 and related markers). Journal: International Journal of Emergency Medicine / related review literature, 2024–2025

GRADE-Based Procalcitonin Guidelines for Emergency Departments

Critical Takeaways:

• Stewardship Utility: PCT is highly effective in guiding antibiotic initiation for lower respiratory tract infections (threshold >0.25 ng/mL) and acute pancreatitis (threshold >1.0 ng/mL).
• Diagnostic Limitations: Evidence does not support using PCT as a standalone marker for diagnosing sepsis; it must be integrated with clinical scores like qSOFA or SIRS.
• Clinical Caveats: Certain conditions significantly alter PCT performance. Surgeons and clinicians should expect false positives in gastrointestinal surgery patients and false negatives in cases of neutropenia, systemic lupus erythematosus (SLE), and infective endocarditis.
• Special Populations: While liver cirrhosis does not significantly impair PCT diagnostic performance, patients on hemodialysis require higher thresholds (e.g., >1.5 ng/mL for confirmation).
• Molecular Integration: Combining PCT with multiplex molecular testing for respiratory viruses is a powerful strategy for distinguishing viral from bacterial etiologies and reducing unnecessary antibiotic use.

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Procalcitonin is a 116-amino acid precursor of calcitonin. In healthy individuals, levels are typically undetectable (<0.01 ng/mL). However, in response to endotoxins and bacterial infections, PCT is rapidly produced by solid organ tissues.

• Kinetics: PCT can be detected within 2–4 hours of infection.
• Half-life: It has a half-life of approximately 24 hours in the body.
• Diagnostic Advantage: Unlike white blood cell counts or image findings, PCT is generally not elevated by viral infections or non-infectious inflammatory responses, though exceptions exist.

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• Lower Respiratory Tract Infections (LRTI): Clinicians should use antibiotics when PCT > 0.25 ng/mL. Meta-analyses show PCT guidance reduces antibiotic use and side effects without increasing 30-day mortality. (Moderate Evidence, Strong Recommendation).
• COPD Exacerbations: Using PCT alone may not reduce prescriptions or improve outcomes due to a high rate of false negatives (54% sensitivity). (Moderate Evidence, Moderate Recommendation).
• Acute Heart Failure: PCT should not be used as a guide for antibiotic prescription in suspected heart failure patients, as it does not alter prescribing behavior or outcomes. (High Evidence, Strong Recommendation).

• General Fever: Evidence does not support relying on a single PCT value of 0.5 ng/mL to initiate antibiotics in febrile ED patients. (High Evidence, Strong Recommendation).
• Pyelonephritis: For patients with fever and pyuria, PCT-guided management (threshold 0.25 ng/mL) significantly reduces antibiotic usage without affecting prognosis. (Moderate Evidence, Moderate Recommendation).
• Acute Pancreatitis: PCT is a critical tool for distinguishing simple inflammation from bacterial infection. Antibiotics are recommended if PCT > 1.0 ng/mL. (High Evidence, Strong Recommendation).

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• Hemodialysis: PCT remains a valid marker, but thresholds must be adjusted. A threshold of >1.5 ng/mL is suggested for confirmation, while 0.85 ng/mL may be used for exclusion. (Low Evidence, Strong/Weak Recommendation).
• Peritoneal Dialysis: PCT has high specificity (0.91) but low sensitivity (0.53) for peritonitis; it is useful for confirmation but not for exclusion. (Moderate Evidence, Moderate Recommendation).
• Liver Cirrhosis: PCT performs well even in patients with cirrhosis.
• Solid Organ Transplant: PCT has moderate sensitivity (0.85) and specificity (0.81) for infectious complications, consistent with non-transplant patients

• Hematopoietic Stem-Cell Transplant: PCT is not supported as a diagnostic tool

----------Primary reference: Lee, Chien-Chang, et al. "GRADE-based procalcitonin guideline for emergency departments." The American Journal of Emergency Medicine 89 (2025): 109-123.

The FLUID type Trial: Comparison of Lactated Ringer’s Solution versus Normal Saline

The FLUID trial was a large-scale, pragmatic, cluster-randomized, crossover trial conducted to determine whether the routine use of lactated Ringer’s solution is clinically superior to normal saline for intravenous administration in hospitalized patients. Conducted across seven hospitals in Ontario, Canada, the study analyzed 43,626 eligible patients to assess the impact of these fluids on a composite primary outcome of death or hospital readmission within 90 days of the index admission.

The trial concluded that a hospital-wide policy favoring lactated Ringer’s solution did not result in a significantly lower incidence of death or readmission compared to normal saline. The incidence of the primary outcome was 20.3% in the lactated Ringer’s group and 21.4% in the normal saline group, a difference that was not statistically significant (P = 0.35). While the study was interrupted by the COVID-19 pandemic—reducing its statistical power—the results across all secondary outcomes remained consistent with the primary findings, showing no significant clinical advantage for balanced crystalloids in a general hospital population.---------

The trial employed an open-label, two-period, two-sequence, cross-sectional, cluster-randomized, crossover design.

• Cluster Definition: Each participating hospital was defined as a cluster.
• Intervention: Hospitals were assigned to use either lactated Ringer’s or normal saline hospital-wide for a 12-week period.
• Crossover: After a washout period, hospitals switched to the alternative fluid for another 12-week period.
• Adherence: Inventory was monitored daily to ensure the assigned fluid accounted for at least 80% of the crystalloid stock. Automatic substitution orders were implemented in both electronic and manual order systems.

1. Stocking/Run-in (1–3 weeks): Time for inventory adjustment and staff education.
2. Active Period 1 (12 weeks): Use of first assigned fluid.
3. Washout (1–2 weeks): No new patients included; allowed for discharge of Period 1 patients to prevent carryover effects.
4. Active Period 2 (12 weeks): Use of second assigned fluid.

Patient data were retrieved from health administrative databases at ICES (formerly the Institute for Clinical Evaluative Sciences). Because the intervention was implemented at the system level, individual patient consent was waived, and analysis was conducted using an intention-to-treat principle at the hospital level.---------

The composite outcome of death or readmission within 90 days showed no statistically significant difference between the two treatment groups.

• Lactated Ringer’s Incidence: 20.3%
• Normal Saline Incidence: 21.4%
• Adjusted Absolute Difference: -0.53 percentage points (95% CI, -1.85 to 0.79; P = 0.35).
• Adjusted Relative Risk: 0.97 (95% CI, 0.90 to 1.05).

Secondary outcomes were consistent with the primary findings, demonstrating no clear superiority for either fluid across various clinical metrics.

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The trial examined several prespecified subgroups to identify if specific populations benefited more from one fluid type.

• Age Groups: Results were generally consistent across ages, though patients over 80 years showed a slightly lower incidence of the primary outcome with lactated Ringer’s (34.9% vs. 38.3%).
• Specialty Subgroups: Outcomes for medicine, surgery, and mental health patients showed no significant divergence from the overall results.
• High-Acuity Groups: Subgroups with sepsis (437 patients) and traumatic brain injury (90 patients) were too small for definitive conclusions, but their results aligned with the main trial findings.
• Sensitivity: Excluding obstetric, elective surgery, or psychiatric patients did not alter the estimated treatment effect.

Primary source: McIntyre, Lauralyn, et al. "A Crossover Trial of Hospital-Wide Lactated Ringer’s Solution versus Normal Saline." New England Journal of Medicine (2025).

The PROCAMIO Trial: Intravenous Procainamide vs. Amiodarone for Tolerated Wide QRS Tachycardia

The PROCAMIO study is a multicentre, randomized, open-labelled trial comparing the safety and efficacy of intravenous (IV) procainamide and IV amiodarone in the acute treatment of haemodynamically stable, sustained monomorphic wide QRS complex tachycardia (presumed to be ventricular tachycardia).

The trial provides high-level evidence that procainamide is significantly safer and more effective than amiodarone in this clinical context. Patients treated with procainamide experienced a significantly lower incidence of major cardiac adverse events (9% vs. 41%) and a significantly higher rate of tachycardia termination (67% vs. 38%) within the 40-minute study period. These findings remained consistent even among the high-risk subgroup of patients with known structural heart disease.--------

Episode Summary: In this Lit Hit, we break down the PROCAMIO trial and highlight the key evidence emergency clinicians need for rapid, informed decision-making when treating stable wide QRS tachycardia. This short episode delivers high-yield takeaways you can apply on your next shift.

• Safety Superiority: Procainamide is associated with a significantly lower risk of major cardiac adverse events—specifically severe hypotension requiring electrical cardioversion—compared to amiodarone.
• Efficacy Advantage: Procainamide is more likely to successfully terminate stable wide QRS tachycardia within 40 minutes than amiodarone.
• Structural Heart Disease: The safety benefits of procainamide extend to patients with structural heart disease, a group often considered high-risk for antiarrhythmic complications.
• Dosing Protocols: Understand the specific regimens used: Procainamide (10 mg/kg over 20 min) and Amiodarone (5 mg/kg over 20 min).
• Clinical Tip: While guidelines have historically listed both drugs with Class II recommendations, PROCAMIO suggests procainamide should be the preferred pharmacological choice for hemodynamically stable wide complex tachycardia. If pharmacological therapy fails or instability develops, immediate electrical cardioversion remains the definitive treatment.

Primary Reference: Ortiz M, Martín A, Arribas F, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. European Heart Journal. 2017;38(17):1329-1335.

ESETT

The trial was designed to determine the most effective second-line treatment for patients with convulsive status epilepticus that is refractory to initial benzodiazepine therapy.

The primary conclusion of the trial is that the three commonly used anticonvulsant drugs—levetiracetam, fosphenytoin, and valproate—are equally effective and have comparable safety profiles.

Furthermore, the incidence of serious adverse events, including life-threatening hypotension, cardiac arrhythmia, and the need for endotracheal intubation, did not differ significantly across the three groups.

Primary Objective: To compare the efficacy and safety of intravenous levetiracetam, fosphenytoin, and valproate in children and adults with convulsive status epilepticus that has not responded to treatment with benzodiazepines.

Trial Name: Established Status Epilepticus Treatment Trial (ESETT)

Design and Methodology:

• Type: A multicenter, randomized, blinded, adaptive comparative-effectiveness trial conducted at 57 hospital emergency departments in the United States.
• Population: The trial enrolled 384 unique patients, aged 2 years and older, who continued to have generalized convulsive seizures after receiving an adequate cumulative dose of benzodiazepines.
• Randomization: Patients were initially randomized in a 1:1:1 ratio. The trial design incorporated response-adaptive randomization, which was intended to adjust assignment probabilities to favor more effective treatments after 300 patients were enrolled.
• Blinding: The trial drugs were identical in appearance, packaging, and administration to maintain blinding for patients, clinicians, and investigators.

The authors noted several limitations that provide important context for the results:

• Early Stoppage for Futility: The trial was stopped after a planned interim analysis concluded there was only a 1% chance of identifying a superior or inferior treatment if enrollment continued.
• Clinical Outcome Assessment: The primary outcome was based on clinical observation of seizures and responsiveness, not electroencephalography (EEG). This makes it difficult to distinguish postictal sedation from ongoing non-convulsive status epilepticus in some patients who failed to meet the primary outcome.
• Inclusion of Non-Epileptic Seizures: A retrospective review by a clinical phenomenology core determined that 10% of enrolled patients had psychogenic nonepileptic seizures.
• Fosphenytoin Dosing: The 10-minute infusion constraint limited the maximum dose of fosphenytoin to 1500 mgPE, which may be a submaximal dose for patients weighing over 75 kg.
• Protocol Deviations: Due to the emergency setting, 27% of enrollments had deviations from eligibility criteria, primarily related to the timing or dosage of the initial benzodiazepine treatment. However, a per-protocol analysis yielded results consistent with the primary intention-to-treat analysis.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1905795

In this Lit Hit, we break down the Thrombosis Canada guide on the Diagnosis of DVT and PE in Pregnancy and highlight the key evidence emergency clinicians need for rapid, informed decision-making. Pregnancy is a well-established risk factor for venous thromboembolism (VTE). Since symptoms that mimic VTE (like leg swelling and dyspnea) are common in normal pregnancy, it is vital to balance a low threshold for investigation with strategies that accurately exclude disease to avoid unnecessary, prolonged anticoagulation. This short episode delivers high-yield takeaways you can apply on your next shift.

What You’ll Learn:

• Risk Context: The daily risk of VTE is increased 5- to 10-fold during pregnancy and 15- to 35-fold early after delivery compared to non-pregnant women of similar age.
• DVT Presentation: The presentation of DVT in pregnancy often differs from non-pregnant patients; the left leg is affected in over 80% of cases. Pregnant patients are more likely to present with isolated iliac and/or femoral vein thrombosis, which may manifest as swelling of the entire leg accompanied by flank, buttock, or back pain.
• Diagnostic Threshold: Because the consequences of failing to diagnose VTE are significant, the threshold for investigating pregnant women with suspected DVT or PE must be low.
• DVT Primary Imaging: Compression ultrasound is the first choice for DVT investigation as it is safe and readily available. The ultrasound should visualize the entire proximal venous system from the iliac to the popliteal vein.
• DVT Repeat Testing: If the initial compression ultrasound (including iliac imaging) is negative, additional testing is generally recommended, typically involving repeating the ultrasound examination twice within 7 days (e.g., days 3 and 7).
• DVT Advanced Imaging: If ultrasound visualization of the iliac system is limited and symptoms suggest isolated iliac vein thrombosis, MRI should be considered if available.
• PE Diagnostic Strategy: The pregnancy-adapted YEARS protocol is the best validated method for diagnosing and excluding PE in pregnancy.
• D-Dimer Utility: While D-dimers increase through normal pregnancy, they are highly sensitive and possess a high negative predictive value (100%) for ruling out VTE, supporting their use in diagnostic algorithms.
• YEARS Protocol: This algorithm combines D-dimer testing with the YEARS criteria (clinical signs of DVT, hemoptysis, and PE as most likely diagnosis). The D-dimer threshold for excluding PE is 1000 ng/mL if the patient has no positive YEARS criteria, but only 500 ng/mL if the patient has one or more positive criteria.
• Fetal Radiation Safety: The calculated radiation dose to the fetus from diagnostic imaging options like V/Q lung scan (0.2–0.7 mGy) and CT pulmonary angiography (CTPA) (0.002–0.51 mGy) is well below the 50 mGy threshold associated with increased fetal health risks.
• Key Controversy/Clinical Tip: Physicians must weigh the potential radiation risks to the mother and fetus against the clinical likelihood of PE. CTPA results in a significantly higher radiation dose to the maternal breast (10 to 70 mGy) compared to V/Q scanning (<1.5 mGy). Some physicians prefer V/Q scanning, especially in women with normal chest radiography, due to theoretical concerns of increased maternal breast cancer risk. If DVT or PE is suspected postpartum, the patient should be investigated as a non-pregnant patient, recognizing this is the highest risk time for VTE.

Primary Reference:Van der Pol LM, et al. Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism. N Engl J Med 2019;380:1139-1149.

Additional Resources:

Thrombosis Canada www.thrombosiscanada.ca

The DVT diagnostic approach is adapted from the Society of Obstetricians and Gynaecologists of Canada (SOGC) Clinical Practice Guideline.