Pharmacodynamic Analysis of the Influence of Propofol on Left Ventricular Long-Axis Systolic Performance in Cardiac Surgical Patients

BACKGROUND: Propofol induced a decline in the left ventricular (LV) systolic performance in non-cardiac surgery. We tested the hypothesis that propofol decreased the LV contractile function by dose dependent manner in cardiac surgery patients. METHODS: Anesthesia was maintained with target-controlled infusions of propofol and remifentanil in cardiac surgery patients. With a fixed effect-site concentration (Ce) of remifentanil (20 ng/mL) after sternotomy, the Ce of propofol was adjusted to maintain a Bispectral index of 40–60 (Ce1). Mitral annular Doppler tissue image tracings and other echocardiographic variables, including end-diastolic and end-systolic volumes, stroke volume, and mitral inflow pulse wave Doppler profile at Ce1, were recorded using transesophageal echocardiography. Echocardiographic recordings were repeated after the Ce-values of propofol were doubled and tripled at 10-minute intervals (defined as Ce2 and Ce3, respectively). Serial changes in echocardiographic variables for each Ce of propofol were assessed using generalized linear mixed effect modeling. The pharmacodynamic relationship between the Ce of propofol and peak systolic mitral annular velocity (Sm) was analyzed by logistic regression using non-linear mixed effect modeling (NONMEM). RESULTS: Means of Ce1, Ce2, and Ce3 were 0.8, 1.6, and 2.4 μg/mL, respectively, and their means of Sm (95% confidence interval) were 9.7 (9.3–10.2), 8.7 (8.2–9.1), and 7.5 cm/sec (7.0–8.0), respectively (P < 0.01). Ce values of propofol and Sm showed a significant inter-correlation and predictability (intercept, 10.8; slope–1.0 in generalized mixed linear modeling; P < 0.01). Ce values producing 10% and 20% decline of Sm with 50%-probability were 1.4 and 2.1 μg/mL, respectively. CONCLUSION: Propofol reduces LV systolic long-axis performance in a dose-dependent manner. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01826149