The effect of midazolam and its reversal flumazenil on sedative and cardiopulmonary variables in sheep

Abstract

The aim of this study was to investigate the effects of flumazenil antagonism after midazolam administration on sedative and cardiopulmonary variables in ewes. Six Awassi ewes were studied at least 14 days apart. The ewes were randomly divided into two groups as midazolam/saline (MDS) and midazolam/flumazenil (MDF). Hemodynamic values, blood gas, metabolic and electrolyte variables and reflex values were determined in both groups before midazolam (0.6 mg/kg, IV) administration (baseline) and after the 5th (T5) and 25th min (T25) of administration. At T25, saline was injected into the MDS and flumazenil (0.02 mg/kg, IV) into the MDF. The same measurements were repeated at the 5th min (T30), 35th min (T60), and 65th min (T90) of saline and flumazenil applications. Midazolam produced deep sedation and a significant increase in reflex scores in both groups at the indicated times (P<0.05). It caused an increase in heart rate (HR), a decrease in systemic and diastolic arterial pressure (SAP, DAP), hypoventilation, mild respiratory acidosis, and adverse effects on metabolic variables at a transient and clinically acceptable level. It was observed that these effects returned to baseline within 5 min with the use of flumazenil in MDF. Flumazenil (0.02 mg/kg, IV) was sufficient to reverse cardiopulmonary adverse effects within 5 minutes during deep sedation by high-dose midazolam (0.6 mg/kg, IV) in ewes.

Keywords

• cardiopulmonary
• flumazenil
• midazolam
• sedation
• sheep