Pharmacodynamics

European Journal of Clinical Pharmacology

, Volume 63, Issue 3, pp 243-252

First online:

Age and sex-related differences in dose-dependent hemodynamic response to landiolol hydrochloride during general anesthesia

  • Ju MizunoAffiliated withDepartrment of Anesthesiology, Faculty of Medicine, The University of Tokyo Email author 
  • , Ikuto YoshiyaAffiliated withHoshigaoka Koseinenkin Hospital
  • , Takeshi YokoyamaAffiliated withDepartrment of Anesthesiology, Faculty of Medicine, The University of Tokyo
  • , Yoshitsugu YamadaAffiliated withDepartrment of Anesthesiology, Faculty of Medicine, The University of Tokyo
  • , Hideko AritaAffiliated withDepartrment of Anesthesiology, Faculty of Medicine, The University of Tokyo
  • , Kazuo HanaokaAffiliated withDepartrment of Anesthesiology, Faculty of Medicine, The University of Tokyo

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Abstract

Objective

Landiolol hydrochloride is a new ultra-short-acting β1-adrenergic receptor blocking agent that is used for patients with tachycardia during general anesthesia. The hemodynamic response to a β-adrenergic receptor blocking agent is generally dependent on the subject. In the present investigation we investigated the effects of age and sex on the hemodynamic response to different doses of landiolol.

Methods

Following a persistence of tachycardia for more than 1 min, landiolol was infused at 0.03125, 0.0625 and 0.125 mg kg−1 min−1 for 1 min followed by 0.01, 0.02 and 0.04 mg kg−1min−1 for 10 min in groups L, M and H, respectively. Heart rate (HR), systolic (sBP) and diastolic blood pressure (dBP) were recorded each minute during the procedure. The respective changes were evaluated using logistic analysis with the equation \( Y{\left( t \right)} = {p + {\left( {q - p} \right)}} \mathord{\left/ {\vphantom {{p + {\left( {q - p} \right)}} {{\left[ {1 + \exp {\left\{ {{\left( {{4m} \mathord{\left/ {\vphantom {{4m} {{\left( {q - p} \right)}}}} \right. \kern-\nulldelimiterspace} {{\left( {q - p} \right)}}} \right)}{\left( {k - t} \right)}} \right\}}} \right]}}}} \right. \kern-\nulldelimiterspace} {{\left[ {1 + \exp {\left\{ {{\left( {{4m} \mathord{\left/ {\vphantom {{4m} {{\left( {q - p} \right)}}}} \right. \kern-\nulldelimiterspace} {{\left( {q - p} \right)}}} \right)}{\left( {k - t} \right)}} \right\}}} \right]}} \), where p, q, m and k indicate the upper asymptote, lower asymptote, maximum slope and time at the maximum slope.

Results

Parameters q and k for HR in group H were smaller than those in group L, whereas the parameters for sBP and dBP were unchanged among the three groups. Parameter q for HR in group H decreased with age of the patient. There was no significant difference in the landiolol-induced change in HR between males and females.

Conclusion

The hemodynamic response to landiolol is reliably modeled by the logistic function, especially in terms of HR. Landiolol causes a rapid and dose-dependent decrease in HR, whereas landiolol-induced changes in sBP and dBP are independent of dose. The landiolol-induced decrease in HR becomes larger with aging, but shows no sex difference. The logistic model may be useful for studying hemodynamic responses to landiolol based on age and sex differences, and may allow development of an improved monitoring system.

Implication statement

The logistic function reliably represents the hemodynamic responses to landiolol. Landiolol reduces HR rapidly and in a dose-dependentl manner whereas landiolol-induced changes in sBP and dBP are independent of dose. A larger decrease in HR is caused by landiolol in elderly patients, but there is no sex difference in the landiolol-induced change in HR.

Keywords

Blood pressure Curve fit Logistic model Tachycardia Ultra short acting β1-adrenergic receptor blocking agent