Midazolam-induced underestimation of mitral regurgitation severity and its pharmacological reversal with flumazenil

Background Sedative agents may alter hemodynamic status and influence the echocardiographic assessment of mitral regurgitation. Although anesthesia-related underestimation of mitral regurgitation has been reported in intraoperative transesophageal echocardiography (TEE), the effects of conscious sedation with midazolam and pharmacologic reversal with flumazenil on mitral regurgitation severity during routine clinical TEE remain incompletely defined. Methods Seventy-four patients with moderate or greater mitral regurgitation (41 primary, 33 secondary) were included. Mitral regurgitation indices, including effective regurgitant orifice area (EROA), regurgitant volume, vena contracta width, and proximal isovelocity surface area (PISA), were assessed on transthoracic echocardiography (TTE) immediately before TEE, after midazolam administration during TEE, and after flumazenil reversal during the same TEE session. Results Midazolam significantly reduced heart rate and blood pressure in both groups. In patients with primary mitral regurgitation, baseline, postmidazolam, and postflumazenil measurements were as follows: EROA 0.31 ± 0.14, 0.25 ± 0.12, and 0.36 ± 0.14 cm 2 ; regurgitant volume 46.71 ± 14.95, 40.76 ± 16.90, and 59.44 ± 18.11 mL; vena contracta width 5.30 ± 1.06, 4.86 ± 1.05, and 5.82 ± 1.16 mm (all P < 0.001). In secondary mitral regurgitation, corresponding measurements were EROA 0.29 ± 0.06, 0.23 ± 0.08, and 0.34 ± 0.10 cm 2 ; regurgitant volume 44.76 ± 11.95, 36.18 ± 11.96, and 57.18 ± 17.96 ml; and vena contracta width 5.24 ± 0.78, 4.61 ± 0.77, and 5.82 ± 0.87 mm, respectively (all P < 0.001). Following midazolam administration, mitral regurgitation severity decreased by half a grade in 61% of patients. After flumazenil administration, vital parameters returned to levels comparable to baseline, and mitral regurgitation severity increased by half a grade in 68% of patients. Conclusion Midazolam is associated with reduced echocardiographic mitral regurgitation severity during TEE, likely through sedation-related changes in loading conditions, whereas flumazenil reverses these changes. Differences between baseline TTE and postflumazenil TEE measurements should be interpreted in light of both recovery from sedation and known modality-related differences between TTE and TEE. Sedation status should therefore be considered when interpreting mitral regurgitation severity during TEE, particularly in patients near clinical decision thresholds.