Dose: 10 to 20 mcg/kg IV
as loading dose
5 to 50 mcg/kg/hour as a continuous infusion
Flumazenil
| Dose: 10 to 20 mcg/kg IV
as loading dose |
| Comments: Flumazenil is used to reverse the effects of benzodiazepines and has no effect on opioids. The dose should be given over 15 to 30 seconds and may need to be repeated since its effects typically last only 30 to 60 minutes and several benzodiazepines have much longer half-lives. Weinbroum (Drug Safety 1997; 17:181) reported that incremental intravenous bolus injections of flumazenil 0.1 to 0.3 mg are the most effective and well tolerated in the diagnosis and treatment of pure benzodiazepine overdose. Intravenous flumazenil 10 to 20 micrograms/kg is effective in neonates and small children. While flumazenil is not associated with haemodynamic adverse effects, caution should be exercised when using this agent in patients who have received chloral hydrate or carbamazepine or whose ECG shows abnormalities typical to those seen after overdose with tricyclic antidepressants (TCAs); the use of flumazenil in the presence of these drugs can sometimes induce treatable cardiac dysrrhythmia. Zaw (Pharmacotherapy 2001; 21:642) reported that flumazenil may also reverse the myoclonic movements following the administration of midazolam. More comments on flumazenil. |
| Toxicity: No information is available on toxicity in infants. The studies sited in the comments on flumazenil reported no significant adverse effects attributable to flumazenil. Most of problems seen in adults were due to the onset of seizures after multi-drug overdoses or in patients who have developed a physical dependence on the benzodiazepines. Flumazenil should be used cautiously, if at all, in children taking other medications that lower the seizure threshold such as tricyclic antidepressants, theophylline, and isoniazid (J Pediatr 1997; 131:582). Two case reports have noted the occurrence of seizures when flumazenil (0.3 mg) was used to reverse the effects of conscious sedation in the ER (Davis. J Emerg Med 1996; 14:331; and McDuffee. Pediatr Emerg Care 1995; 11:186). The other concern is that respiratory depression may recur after an initial reversal of long-acting benzodiazepines (Facts and Comparisons, Inc. Drug Facts and Comparisons. Olin, B.R. ed. St. Louis, MO:Facts and Comparisons, Inc; 1995, page 710d). |
| Preparation: Flumazenil (Romazicon) is available
in 5 ml vials (100 mcg/ml). If diluted with D5W, LR, or NS, stable at room temperature
for 24 hours. |
|
| Compatibility: Compatible with D5W, LR, or normal saline. Compatibility with TPN and filter is unknown. It is also compatible with aminophylline, dobutamine, dopamine, famotidine, heparin, lidocaine, procainamide, and ranitidine. |
Weight (grams) |
Dose (ml) |
Weight (grams) |
Dose (ml) |
500 |
* |
3000 |
0.30 |
750 |
* |
3250 |
0.33 |
1000 |
0.10 |
3500 |
0.35 |
1250 |
0.13 |
3750 |
0.38 |
1500 |
0.15 |
4000 |
0.40 |
1750 |
0.18 |
4250 |
0.43 |
2000 |
0.20 |
4500 |
0.45 |
2250 |
0.23 |
4750 |
0.48 |
2500 |
0.25 |
5000 |
0.50 |
2750 |
0.28 |
5250 |
0.53 |
* For small doses, add 9 ml of sterile water or saline to 1 ml of the 100 mcg/ml concentration of flumazenil. This gives a concentration of 10 mcg/ml. The dose would be: Wgt (kg) X 10 mcg/kg / 10 mcg/ml. Reconstituted solution stable for 24 hours from the time the initial vial was prepared stored at room temperature.