A healthy 40‑year‑old man underwent outpatient extracorporeal shock‑wave lithotripsy (ESWL) with midazolam, fentanyl, and a propofol bolus; 2–3 hours after discharge he developed severe hypotension (blood pressure 60/40–70/40) without cutaneous or respiratory signs. Is this presentation an anaphylactic reaction or a non‑allergic delayed hypotensive episode?

Delayed Hypotension After ESWL: Unlikely to Be Anaphylaxis

This delayed presentation 2–3 hours post-discharge with isolated severe hypotension and no cutaneous or respiratory signs is highly atypical for anaphylaxis and more consistent with a delayed hemodynamic complication or residual sedative effect. 1

Why This Is Probably NOT Anaphylaxis

Timing Arguments Against Anaphylaxis

• Anaphylaxis typically occurs within minutes of drug administration, though it can be delayed up to 1 hour 1
• Your patient received propofol, midazolam, and fentanyl during the procedure, yet developed hypotension 2–3 hours after leaving the facility—well beyond the typical anaphylaxis window 1
• Propofol anaphylaxis specifically develops rapidly (within 1–2 minutes of administration), as demonstrated in a case where hypotension occurred within 1 minute of propofol injection 2
• Even midazolam-induced anaphylaxis, which can have slightly delayed onset, typically manifests within 17 minutes of administration 3

Clinical Presentation Arguments Against Anaphylaxis

• Hypotension as the sole clinical feature occurs in only approximately 10% of allergic anaphylaxis cases during anesthesia 1
• Cutaneous signs (flushing, urticaria, rash) are present in 71.9% of allergic anaphylaxis cases 1
• Your patient had isolated hypotension without any mention of:
  • Cutaneous flushing or urticaria (present in >70% of cases) 1
  • Bronchospasm or respiratory distress (present in ~40% of cases) 1
  • Angioedema (present in ~12% of cases) 1
  • Tachycardia (though bradycardia occurs in ~10% of anaphylaxis) 1

What This More Likely Represents

Delayed Sedative Effects

• Midazolam has a prolonged elimination half-life that can be substantially extended in certain conditions 4
• The FDA label notes that midazolam clearance is reduced with conditions that diminish cardiac output and hepatic blood flow 4
• Infrequent hypotensive episodes can occur with midazolam, and neither the time to onset nor duration appears related to plasma concentrations 4
• Your dosing regimen (1 mg midazolam + 25 mcg fentanyl every 15–30 minutes over 45 minutes, plus propofol boluses) represents significant cumulative sedation 5

Delayed Hemodynamic Complications

• ESWL can cause serious, potentially life-threatening complications that may present in a delayed fashion 6
• The literature emphasizes that "due to the increasing number of outpatient procedures, careful clinical and ultrasound monitoring with early recognition of complications is necessary after each ESWL therapy" 6
• Delayed presentations can occur hours after the procedure 6

What Should Have Been Done (And What to Do Next Time)

Immediate Diagnostic Steps That Were Missed

• Tryptase levels should have been drawn at specific time points: 1
  • First sample as soon as feasible after onset (ideally within 1 hour)
  • Second sample at 1–2 hours after symptom onset
  • Third sample at 24 hours or later for baseline comparison
• Without tryptase levels, you cannot definitively rule out anaphylaxis retrospectively 1

Proper Management of Severe Hypotension (BP 60/40–70/40)

If you suspect anaphylaxis with Grade III life-threatening hypotension: 1

• Administer IV epinephrine 50 mcg initially if no other vasopressors given 1
• Administer IV epinephrine 100 mcg if unresponsive to other vasopressors 1
• Give crystalloid 1 L as rapid bolus and repeat if inadequate response 1
• If persistent after 10 minutes, add norepinephrine infusion (0.05–0.5 mcg/kg/min) 1

The team appropriately started pressors, which stabilized the patient 1

Critical Observation Period

• Patients should be observed in a monitored area for a minimum of 6 hours or until stable and symptoms are regressing 1
• Your patient was discharged approximately 2–3 hours before the hypotensive episode occurred—highlighting the risk of premature discharge after outpatient ESWL with sedation 7, 6

Common Pitfalls to Avoid

Don't Assume Immediate Reactions Only

• While most anaphylaxis occurs within minutes, substances like antibiotics, IV colloids, and latex can have delayed reactions up to 1 hour 1
• However, 2–3 hours post-discharge exceeds even these delayed timeframes 1

Don't Ignore Cumulative Sedation Effects

• Midazolam can accumulate in peripheral tissues with continuous or repeated dosing 4
• Your incremental dosing strategy over 45 minutes, while appropriate for procedural sedation, can lead to prolonged effects 5
• The elimination half-life of midazolam ranges from 0.78–3.3 hours in healthy adults but can be substantially prolonged (up to 12 hours in compromised patients) 4

Don't Skip Post-Procedure Monitoring

• Outpatient ESWL requires careful clinical monitoring with early recognition of complications 6
• The shift to >90% outpatient procedures increases the risk of delayed complications presenting after discharge 7

Definitive Answer for Future Cases

For your specific question about propofol anaphylaxis timing: No, if this were propofol anaphylaxis, it would have manifested within 1–2 minutes of administration, not 2–3 hours later 2. The case report of propofol/fentanyl anaphylaxis showed hypotension developing within 1 minute, with facial edema and generalized wheals by 2 minutes 2.

Most likely diagnosis: Delayed hemodynamic instability from cumulative sedative effects (midazolam/fentanyl) or an unrecognized ESWL complication, NOT anaphylaxis 4, 6.

What you should have documented: Absence of cutaneous signs, respiratory symptoms, and tryptase levels to definitively exclude anaphylaxis 1.