Choosing Routes, Managing Risk

This episode explores how the choice of IV, IM, or PO routes can meaningfully change medication effectiveness, safety, and patient experience in the emergency department. Through core pharmacologic principles and common real-world pitfalls, the discussion highlights when route truly matters and how to avoid silent errors that delay care. Listeners will leave with practical medication-specific insights they can apply during their next shift.  Then, in this edition of Legal Lessons, Kelly and Micaela review a case of a missed DVT that resulted in a PE in a patient who had a recent fracture. The twist is that the doctor is friends with the patient. Micaela and Kelly explore the social pressures that may have contributed to this missed diagnosis.

 

Medication Route Matters

Sara Divello, PharmD and Geoff Comp, DO

 

Pearls:

• Match the route to urgency and physiology—IV, IM, and PO differ substantially in onset, reliability, and risk depending on perfusion and clinical context.
• Many stable ED patients can safely receive PO medications with outcomes equivalent to IV therapy, improving flow and avoiding unnecessary procedures.
• IM medications are often less predictable than clinicians assume—particularly in hypotension, vasoconstriction, obesity, and when dose stacking occurs. Thoughtful route selection improves both safety and patient experience.

Background:

• IV, IM, and PO are the three main medication administration routes used in the ED.
• Others, like transdermal, rectal,  or endotracheal, exist but get less use (perhaps except for nebulized meds for our COPD or asthma populations)
• Each of these routes will have its benefits and drawbacks, and selecting which route to use is often as important as selecting which medication to use.

 

Selecting the best route: Benefits and Drawbacks of IV, IM, and PO

• IV
• IV is the most predictable route: 100% bioavailable, immediate bloodstream delivery, and fastest onset—when access is feasible.
• IV is also the fastest route in terms of onset.
• However, IV administration can be more time-consuming or more challenging, 
• Especially in agitated patients, pediatrics, or patients with difficult IV access.
• IM
• IM can be your friend when IV isn’t feasible or isn’t appropriate for the patient scenario (e.g., epi in anaphylaxis, vomiting patient who is likely being discharged).
• However, reliability hinges on perfusion and site. 
• The thigh (vastus lateralis) is preferred for speed/safety
• Bigger muscle mass, Better perfusion
• Having adequate muscle mass is important, as having adequate perfusion makes the onset more reliable.
• Sometimes, frail or elderly patients don’t have enough muscle mass to make IM reliable.
• Avoid IM in hypotension or vasopressor-related vasoconstriction
• Absorption and onset are unreliable in these scenarios, making IM a less ideal choice for these patients.
• PO
• Often, this is the right choice for stable/cooperative patients.
• PO is more appropriate for many patients with less emergent complaints or those who will likely be discharged rapidly.
• Absorption can be compromised by delayed gastric emptying (e.g., GLP-1 agonists) or altered GI anatomy (e.g., bariatric surgery).

Special situations with IM administration:

• There are some patients for whom IM will be the preferred route, and each comes with its own caveats and considerations.
• The two most common scenarios in Emergency Medicine where IM is the preferred route are agitated patients and anaphylaxis.
• In obese patients, IM can be more difficult.
• Medications sometimes end up being subQ instead of IM, leading to irregular absorption and onset.

 

The agitated patient:

• For agitated patients, IV and PO medications are often not feasible, making IM the preferred route for patient and staff safety as well as efficacy and efficiency of getting control of the situation.
• In agitated patients, the vastus lateralus is the preferred site due to its size and vascularity.
• These patients rarely experience poor perfusion, so IM onset is generally reliable.
• Midazolam is the IM benzodiazepine of choice for agitated patients. 
• It has faster absorption and onset, has more reliable absorption, and crosses the blood-brain barrier faster.
• Lorazepam has slow and less reliable absorption and takes longer to cross the blood-brain barrier.
• Wait at least 5 minutes between IM doses of midazolam.
• Dose stacking can occur when you don’t wait long enough, but waiting minutes can feel like a very long time when trying to control agitated patients, so you have to be intentional with the dose timing.

 

Anaphylaxis:

• IM administration is preferred in anaphylaxis due to the rapidity of administration and ease/familiarity of dosing.
• Vastus lateralus is the preferred site due to muscle mass and increased perfusion, leading to higher serum concentration more quickly.

 

Bioavailability and First Pass Metabolism:

• Definitions
• Bioavailability: The fraction of a drug dose that is available to exert the desired systemic effect.
• First-pass metabolism: Oral drugs pass through the liver before exerting systemic effects and may be deactivated in the liver before reaching systemic circulation
• This explains why some oral doses must be much higher than IV doses
• e.g., 4mg IV morphine ≈ 10 mg PO morphine (~40% bioavailable)
• When oral dosing is much higher than IV dosing, that’s a clue that the bioavailability is low.
• IV as a reference point
• IV medications are considered 100% bioavailable because they bypass GI/liver first pass

When PO is the way to go:

• Sometimes oral medications are equally effective and faster to administer than IV or IM medications.
• Examples include ODT ondansteron for vomiting patients or oral dexamethasone for pediatric patients.
• Both have good bioavailability, and giving them PO rather than IV or IM will lead to similar onset and increased patient satisfaction.
• One caveat or exception may be with IM  penicillin G benzathine (when available) for diseases like strep throat.
• This can be useful in pediatrics, where getting them to take meds regularly can be challenging, as well as in homeless or other at-risk populations, where follow-through and follow-up are challenging.

 

Rapid Fire Myth Busting:

• Most overrated IV medication
• IV acetaminophen (costly; no 1-hour pain benefit difference vs PO noted)
• PO medication is more effective than many realize
• Oxycodone (onset discussed as 15–30 minutes)
• IM medication that underperforms most often
• IM opioids (painful injection + variable absorption; if able to take PO, oxycodone will have better bioavailability and may be a better choice)

References:

1. Fosnocht DE, Hollifield MB, Swanson ER. Patient preference for route of pain medication delivery. J Emerg Med. 2004;26(1):7-11. PMID: 14751473
2. MacGregor RR, Graziani AL. Oral administration of antibiotics: a rational alternative to the parenteral route. Clin Infect Dis. 1997;24(3):457-467. PMID: 9114201
3. Parker SE, Davey PG. Pharmacoeconomics of intravenous drug administration. Pharmacoeconomics. 1992;1(2):103-115.  PMID: 10146940
4. Shatsky M. Evidence for the use of intramuscular injections in outpatient practice. Am Fam Physician. 2009;79(4):297-300. PMID: 19235496
5. Eftekhari K, Mohammadpour S, Shahgholi E, Shabani Mirzaee H, Vigeh M, et al. Oral Versus Intramuscular Ondansetron for Reducing Vomiting in Children with Acute Gastroenteritis: A Single-Blind Randomized Clinical Trial.Inn J Pediatr.2020;31(1):e106115.https://doi.org/10.5812/ijp.106115.
6. Simons FER, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001;108(5): 871-73. PMID: 11692118
7. Berkelhamer SK, Vali P, Nair J, et al. Inadequate bioavailability of intramuscular epinephrine in a neonatal asphyxia model. Front Pediatr. 2022 Feb 21;10:828130. PMID: 35265564.
8. Erstad BL, Barletta JF. Implications of obesity for drug administration and absorption from subcutaneous and intramuscular injections: A primer, American Journal of Health-System Pharmacy, Volume 79, Issue 15, 1 August 2022, Pages 1236–1244, https://doi.org/10.1093/ajhp/zxac058

 

Legal Lessons:  Friend or Patient?

Kelly Heidedpriem, MD and Micaela Bowers, MD

 

Pearls

• Avoid serving as the primary clinician for friends or family whenever possible—blurred boundaries increase the risk of cognitive bias, missed history, and shared liability.
• Calf pain after lower extremity injury and immobilization—especially in a patient with prior DVT or strong family history—demands formal VTE risk stratification (e.g., Wells score) and consideration of imaging. Clinical gestalt alone is insufficient.
• Referring a friend or patient to a colleague does not eliminate liability. If you are involved in the care or aware of concerning symptoms, you may still share responsibility if appropriate follow-up or oversight does not occur.

 

Case Overview

• Case sourced from the MedMal Reviewer website, which analyzes real malpractice cases using court records and expert testimony.
• Focus: Legal and clinical lessons from a missed DVT/PE in a patient treated by her friend/PCP.

 

Clinical Timeline

• Initial Injury:
• Mary, who had been seeing her friend (Dr. S) as her PCP for ~2 years, injured her ankle while hiking with Dr. S.
• The next day, she was evaluated in the clinic by an APP.
• X-ray: Non-displaced transverse fracture of the lateral malleolus.
• Treatment: CAM walker boot; follow-up in 3 weeks.
• Management at this stage was appropriate.
• New Symptom: Calf Pain
• Three days later, Mary reported calf soreness and tightness.
• Message was left via the office (unclear if directly to Dr. S).
• Dr. S advised her to see colleague Dr. C.
• Three days after that, she was evaluated by Dr. C.
• Relevant History
• Personal history of DVT and thrombophlebitis.
• Family history: Mother and brother with pulmonary emboli.
• Assessment by Dr. C
• Diagnosed with tightness of heel cord/Achilles.
• Advised massage, continued CAM boot, and 3-week follow-up.
• No DVT workup performed.
• Clinical Deterioration
• Four days after the clinic visit, Mary developed lightheadedness and suffered cardiac arrest.
• Found unresponsive by husband; CPR initiated.
• ROSC was achieved at the hospital.
• CT scan: Bilateral pulmonary emboli with a large clot burden.
• Hospitalized 8 days; 1 additional week in rehab.
• Survived.
• Legal Claims
• Allegations Against Dr. C
• Failed to recognize the seriousness of calf pain.
• Failed to identify DVT risk.
• Fell below the standard of care.
• Cardiac arrest and sequelae were the direct result of negligence.
• Allegations Against Dr. S (Friend/PCP)
• Was aware of calf symptoms.
• As PCP, allegedly had a duty to ensure appropriate evaluation and studies.
• Failure to ensure DVT workup constituted negligence.
• Key Point:
• Even though Dr. S referred the patient to a colleague and did not personally evaluate her, the complaint alleged shared responsibility due to involvement and existing PCP relationship.

 

Understanding the Legal Process

• Tone of a Complaint
• Initial complaint language is accusatory and direct.
• Designed to assign blame and frame negligence.
• It is important for clinicians to understand that this tone is standard—not personal.
• Regarding Dr C., the complaint reads: (SEE DOWNLOADABLE CONTENT)

• Damages Claimed
• Lifelong anticoagulation requirement.
• Loss of opportunity to obtain life insurance.
• Economic and non-economic damages.
• Economic vs. Non-Economic Damages
• Some states cap non-economic damages (e.g., pain and suffering).
• Economic damages (medical bills, future care) often uncapped.
• Plaintiffs may attempt to categorize long-term medication costs as economic damages to increase ceiling.
• Settlement
• Plaintiffs offered to settle for $850,000 from each defendant and hospital system.
• Confidential settlement reached; lawsuit withdrawn.
• Settlements are often lower than initial demand.

 

Medical Analysis

• DVT Risk After Immobilization
• Below-knee immobilization increases VTE risk (~8-fold increase per cited discussion).
• Estimated absolute risk in one study: ~2.2%.
• Risk compounded by:

• Prior DVT
• Strong family history of PE
• Acute fracture
• Immobilization

Diagnostic Approach

• Isolated findings (e.g., absence of swelling) are insufficient to rule out DVT.
• Formal risk stratification (e.g., Wells score) recommended.
• Must first suspect DVT to apply risk tools appropriately.
• Clinical Pearl:  Patients do not always present “by the textbook.” Calf discomfort near fracture site does not exclude DVT.

 

Anticoagulation and Cost Considerations

• Provoked vs. Recurrent VTE
• This DVT was provoked (fracture + immobilization).
• However, prior DVT history complicates long-term management decisions.
• Recurrent events may warrant extended or lifelong anticoagulation.
• Cost Estimates
• Estimated lifetime therapy cost (40 years, AFib model comparison).
• Warfarin: ~$16,000
• Apixaban: ~$77,000
• Warfarin adds INR monitoring burden and associated indirect costs.
• Legal Relevance: Determining whether lifetime anticoagulation is directly attributable to the alleged negligence affects economic damage calculations.

 

Treating Friends and Family: Ethical and Legal Pitfalls

• Professional Guidance:
• ACP and AMA recommend avoiding routine care of friends and family.
• Risks include:
• Cognitive bias
• Failure to ask sensitive questions
• Assumptions about shared knowledge
• Boundary violations
• Common Realities:  
• Many clinicians provide informal advice via text or phone.
• Boundaries often blur in small communities.
• Cognitive Risk in This Case
• Possible assumptions:
• Patient assumed PCP remembered prior DVT.
• PCP may not have recalled full thrombotic history.
• Lack of explicit documentation and formal evaluation increases risk.

 

Practical Takeaways for Clinicians

• Establish Personal Boundaries:
• Consider firm rules (e.g., no prescribing for friends).
• Avoid acting as PCP for close friends if feasible.
• Direct friends to formal evaluation through appropriate channels.
• Close the Loop
• If you are involved—even peripherally—review documentation.
• Confirm diagnosis and follow-up plan.
• Similar principle to reviewing finalized radiology reads.
• Apply Risk Stratification Consistently
• Calf pain + immobilization + prior DVT = automatic DVT consideration.
• Use Wells score or structured assessment.
• Do not rely solely on gestalt or proximity to injury site.
• Recognize Shared Liability Risk
• Referring to a colleague does not fully insulate you if:
• You are the PCP.
• You were aware of concerning symptoms.
• You had opportunity to intervene.

 

Bottom Line

• This case involved a clear diagnostic miss with significant morbidity.
• Social dynamics likely influenced care but were not part of the legal complaint.
• Treating friends introduces assumptions and blurred accountability.
• Structured risk assessment and deliberate boundary-setting are key to both patient safety and medicolegal protection.

 

References:

1. Chapter 1.2.1 of the AMA Code of Medical Ethics. https://www.ama-assn.org/sites/default/files/media-browser/code-of-medical-ethics-chapter-1.pdf. Accessed January 26, 2026.
2. Goodacre S, Sutton AJ, Sampson FC. Meta-analysis: The value of clinical assessment in the diagnosis of deep venous thrombosis. Ann Intern Med. 2005;143(2):129-139. PMID: 16027455
3. Baglin T, Bauer K, Douketis J, et al. Duration of anticoagulant therapy after a first episode of an unprovoked pulmonary embolus or deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost. 2012;10(4):698-702. PMID: 22332937
4. van Adrichem RA, Debeij J, Nelissen RG, Schipper IB, Rosendaal FR, Cannegieter SC. Below-knee cast immobilization and the risk of venous thrombosis: results from a large population-based case-control study. J Thromb Haemost. 2014;12(9):1461-1469. PMID: 25040873
5. Blanco JA, Slater G, Mangwani J. A Prospective Cohort Study of Symptomatic Venous Thromboembolic Events in Foot and Ankle Trauma: The Need for Stratification in Thromboprophylaxis?. J Foot Ankle Surg. 2018;57(3):484-488. PMID: 29503135
6. Cowper PA, Sheng S, Lopes RD, et al. Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial. JAMA Cardiol. 2017;2(5):525–534. PMID: 28355434