Comparison of routes of flumazenil administration to reverse midazolam-induced respiratory depression in a canine model
| Autor: | Anne Trout, David R. Nelson, Melanie S. Heniff, William H. Cordell, Gregory P. Moore |
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| Rok vydání: | 1997 |
| Předmět: |
Flumazenil
Time Factors Dose Midazolam Antidotes Administration Sublingual Drug Evaluation Preclinical Injections Intramuscular Random Allocation Dogs Administration Rectal Medicine Animals Hypnotics and Sedatives Respiratory system Tidal volume Depression (differential diagnoses) Cross-Over Studies business.industry General Medicine Crossover study Disease Models Animal Anesthesia Injections Intravenous Emergency Medicine Breathing business Respiratory Insufficiency medicine.drug |
| Zdroj: | Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 4(12) |
| ISSN: | 1069-6563 |
| Popis: | OBJECTIVE To determine whether flumazenil, a drug used to reverse benzodiazepine-induced respiratory depression and approved only for i.v. use, is effective by alternative routes. METHODS A randomized, controlled, nonblinded, crossover canine trial was performed to evaluate reversal of midazolam-induced respiratory depression by flumazenil when administered by alternative routes. Mongrel dogs were sedated with thiopental 19 mg/kg i.v., then tracheally intubated. With the dogs spontaneously breathing, tidal volume, end-tidal CO2, and O2 saturation were observed until a stable baseline was achieved. Incremental doses of midazolam were administered until respiratory depression (30% decline in tidal volume, 10% decrease in O2 saturation, and 15% increase in end-tidal CO2) occurred. Flumazenil was administered by a randomly selected route [0.2 mg followed 1 minute later by 0.3 mg i.v., sublingual (s.l.) or intramuscular (i.m.); or 1 mg followed 1 minute later by 1.5 mg per rectum (PR)]. Time to return to baseline respiratory functions was recorded ("time to reversal"). Each of 10 dogs was studied using all 4 routes of flumazenil administration with a washout period of at least 7 days. An additional dog served as a control (no flumazenil). RESULTS The control time to reversal was 1,620 seconds. The i.v. route was significantly faster (mean 120 +/- 24.5 sec) than the other 3 routes (p < 0.005). The SL route was the second fastest (mean 262 +/- 94.5 sec), the IM route was the third fastest (mean 310 +/- 133.7 sec) and the PR route was the s;owest (mean 342 +/- 84.4 sec). The SL, IM, and PR routes did not differ significantly from one another. CONCLUSIONS Flumazenil administered by all 4 routes reversed midazolam-induced respiratory depression in a dog model. For the selected dosages used, the i.v. route was significantly faster than all 3 other routes, and SL was the second fastest. |
| Databáze: | OpenAIRE |
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