Introduction
- While verbal de-escalation should always be attempted first, chemical sedation of acutely agitated
- In 2001, the U.S. FDA issued a black-box warning for droperidol and QTc prolongation based on
- The majority of these cases were reported at higher doses than those used in the ED (65-300 mg)
- Multiple prospective studies have demonstrated safe and effective use of droperidol in the ED for
patients may be required if the patient becomes a danger to themselves or to ED staff.
observational after-market data
acute agitation.
Clinical Detail
| Parameter | Detail |
|---|---|
| MOA | Butyrophenone D2 receptor antagonist |
| Dose | 5-10 mg alone 2.5-5 mg coadministered with midazolam |
| Administration | Routes: IM or IV |
| PK/PD | Onset: 3-10 min Peak: ~ 30 min Duration: 2-4 hours |
| Adverse Effects | Mild to moderate hypotension Bradycardia QTc prolongation (dose dependent) Extrapyramidal symptoms (dystonia, akathisia) |
| Drug Interactions and warnings | Pheochromocytoma: may cause severe hypertension or tachycardia Other CNS depressants- potentiating effect |
| Compatibility | Compatible with NS, D5W, or LR |
| Comments | No renal dose adjustments required |
Evidence
| Author, year | Design/ sample size | Intervention & Comparison | Outcome |
|---|---|---|---|
| Martel, 20203 | DB, RCT (n=115) | IM Droperidol 5 mg IM Ziprasidone 10 mg IM Ziprasidone 20 mg IM Lorazepam 2 mg | Droperidol was more effective than ziprasidone 10mg or 20 mg, and lorazepam at 15 minutes 64% compared to 25%, 35%, 29% |
| Cole, 20204 | Observational (n= 16,546) | IV/IM Droperidol | The mean QTc difference was +3.3 milliseconds (ms) after droperidol The incidence of torsades des pointes (TdP) was 1/16,546 or 0.006% |
| Yap et al, 20175 | Subgroup analysis of RCT (n=92) | IV Midazolam 5 mg + IV Droperidol 5 mg IV Droperidol 10 mg IV Olanzapine 10 mg | At 10 minutes, significantly more patients in the midazolam-droperidol group Midazolam-droperidol 85.3% compared to 46.7% droperidol monotherapy, and 50% olanzapine monotherapy |
| Taylor et al. 20176 | RCT (n= 345) | IV midazolam 5 mg + IV droperidol 5 mg IV Droperidol 10 mg IV Olanzapine 10 mg | Midazolam + droperidol was faster than either droperidol or olanzapine alone, and required less rescue doses 76.6% compared to 49.6% and 49.2% respectively |
| Calver 20207 | Observational (n= 1,009) | IM/IV Droperidol 10 mg | Thirteen of 1,009 or 1.3% patients had an abnormal QT Median time to sedation was 20 minutes (IQR 10 to 30 minutes) No cases of torsades de pointes |
| Chan et al. 20138 | DB, RCT (n=336) | IV Droperidol 5 mg + midazolam IV Olanzapine 5 mg + midazolam IV Placebo + midazolam | Combination of droperidol or olanzapine + IV midazolam resulted in faster median time to sedation ( 6, 5 min vs. 10 min) than midazolam monotherapy The 3 groups’ adverse event profiles and lengths of stay did not differ. |
| Isbister et al. 20109 | DB, RCT (n = 91) | IM Midazolam 10 mg IM Droperidol 10 mg IM Droperidol 5 mg + IM midazolam 5 mg | IM droperidol resulted in similar security duration as midazolam or midazolam/droperidol combination, Droperidol required less additional sedation, had a lower rate of adverse effects Droperidol had no cases of arrhythmias or QT prolongation |
| Knott et al. 200610 | DB, RCT (n=74) | IV Midazolam 5 mg IV Droperidol 5 mg | 28.1% more patients were sedated at 5 min with IV midazolam vs. droperidol At 10 min ~ 50% of patients were adequately sedated in both the midazolam and droperidol groups. Less patients in the droperidol group required additional sedation within 60 min vs. midazolam group |
Conclusions
Droperidol appears safe and effective at the low doses required for acute agitation in the ED and results in less respiratory
depression than midazolam monotherapy.
Droperidol does not have to be administered with a benzodiazepine to achieve rapid and adequate sedation
There is a low rate of akathisia with droperidol that can be managed with IV diphenhydramine
References
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