What are the differences between droperidol and Ativan (lorazepam) compared to B52, and why can Benadryl (diphenhydramine) be added to Haldol (haloperidol) but not droperidol?

Understanding B52 vs Droperidol/Ativan and Diphenhydramine Compatibility

What is B52?

B52 is a specific medication cocktail consisting of Benadryl (diphenhydramine) 50mg + Haldol (haloperidol) 5mg + Ativan (lorazepam) 2mg, typically given intramuscularly for acute agitation. 1, 2

Key Differences Between Droperidol/Ativan and B52

Medication Components

• Droperidol + Ativan (lorazepam) is a two-drug combination using a butyrophenone antipsychotic plus a benzodiazepine 1
• B52 is a three-drug combination that adds diphenhydramine (an anticholinergic antihistamine) to haloperidol and lorazepam 1, 2

Efficacy Differences

• Droperidol combinations demonstrate superior speed of sedation compared to haloperidol-based regimens, with droperidol/midazolam achieving adequate sedation in 51.2% of patients at 10 minutes versus only 7% with haloperidol/lorazepam 2
• Median time to adequate sedation is 10 minutes for droperidol/midazolam versus 30 minutes for haloperidol/lorazepam 2
• Droperidol produces significantly lower sedation scores at 10,15,30, and 60 minutes compared to lorazepam alone 3
• Droperidol requires fewer repeat doses (8 patients) compared to lorazepam (40 patients) at 30 minutes 3

Safety Profile

• Both droperidol and haloperidol carry FDA black box warnings regarding QTc prolongation and potential dysrhythmias 4
• Droperidol has demonstrated low adverse event rates (2.9%) comparable to haloperidol combinations 1
• Neither combination shows significant differences in major adverse events including intubation (0.3%), akathisia (0.04%), or dystonia (0.03%) 5

Why Diphenhydramine Can Be Added to Haloperidol But Not Droperidol

The Anticholinergic Rationale

• Diphenhydramine is added to haloperidol specifically to prevent or treat extrapyramidal symptoms (EPS), particularly acute dystonic reactions 4
• Haloperidol carries a significantly higher risk of movement disorders and extrapyramidal symptoms even at low doses 4
• The anticholinergic properties of diphenhydramine counteract the dopamine-blocking effects that cause EPS 4

Why Droperidol Doesn't Need Diphenhydramine

• Droperidol demonstrates "notably absent movement disorders, including extrapyramidal symptoms and dystonia" in clinical trials 4, 6
• High-quality evidence from Cochrane reviews shows no significant increase in extrapyramidal symptoms with droperidol compared to placebo or other agents 6
• In prospective studies, no patients receiving droperidol experienced extrapyramidal symptoms requiring treatment 2

Practical Clinical Algorithm

For acute agitation requiring chemical restraint:

1. First-line: Droperidol 5mg + Midazolam 5mg IM achieves adequate sedation at 10 minutes in >50% of patients 2

   • Expect median sedation time of 10 minutes 2
   • No diphenhydramine needed due to minimal EPS risk 6, 2

2. Alternative: Haloperidol 5mg + Lorazepam 2mg + Diphenhydramine 50mg IM (B52) if droperidol unavailable 1, 2

   • Expect median sedation time of 30 minutes 2
   • Diphenhydramine is essential to prevent dystonic reactions 4

3. Monitor for oxygen supplementation needs: 25.6% of droperidol/midazolam patients may require supplemental oxygen versus 9.3% with haloperidol/lorazepam 2

Common Pitfalls to Avoid

• Do not add diphenhydramine to droperidol routinely - it adds unnecessary anticholinergic burden without addressing a significant EPS risk that doesn't exist with droperidol 6, 2
• Never omit diphenhydramine from haloperidol-based cocktails - haloperidol's high EPS risk makes prophylaxis essential 4
• Droperidol requires fewer repeat doses, so avoid premature re-dosing before 30 minutes 3