Modelling of the Sedative Effects of Propofol in Patients undergoing Spinal Anaesthesia: A Pharmacodynamic Analysis

Abstract

Sedation can increase patient comfort during spinal anaesthesia. Understanding the relationship between the propofol effect-site concentration (Ce) and patient sedation level could help clinicians achieve the desired sedation level with minimal side effects. We aimed to model the relationship between the propofol Ce and adequate and deep sedation and also incorporate covariates. Thirty patients scheduled for orthopaedic surgery received spinal anaesthesia with 0.5% bupivacaine. Propofol was administered via an effect-site target-controlled infusion device using the Schnider pharmacokinetic model. The pharmacodynamic models for both adequate sedation [Observer's Assessment of Alertness/Sedation (OAA/S) scores of 3-4] and deep sedation (OAA/S scores of 1-2) were developed using nonlinear mixed-effects modelling. Increments in the propofol Ce were associated with increased depths of sedation. In the basic model, the estimated population Ce 50 values for adequate and deep sedation were 0.94 and 1.52 lg/ml, respectively. The inclusion of the patient's age and sensory block level for adequate sedation and of age for deep sedation as covariates significantly improved the basic model by decreasing the objective function's minimum value from 10696.72 to 10677.92 (p = 0.0003). The simulated Ce 50 values for adequate sedation in 20-year-old patients with a T 12 sensory level and in 80-year-old patients with a T 4 level were 1.63 and 0.53 lg/ml, respectively. Both age and sensory block level should be considered for adequate sedation, and the propofol concentration should be reduced for elderly patients with a high spinal block to avoid unnecessarily deep levels of sedation.Propofol is one of the most commonly used drugs for sedation during spinal anaesthesia because of its rapid onset, easy titration and rapid offset. However, propofol frequently induces unnecessary deep sedation or side effects such as respiratory and cardiovascular depression because it has a narrow therapeutic range [1][2][3]. The use of a target-controlled infusion (TCI) system for propofol administration allows rapid induction and safe maintenance of the desired level of sedation, thereby making it ideal for technically demanding procedures [4][5][6]. Understanding the concentration-response relationship of sedation is fundamental for the safe use of propofol with incorporating factors influencing the sedative effect. However, few studies have evaluated the quantitative relationship between the effect-site concentration (Ce) of propofol and its sedative effect under spinal anaesthesia, although propofol is considered to induce sedation in a dose-dependent manner [7]. Therefore, we attempted to model the relationship between propofol Ce and sedation and also to characterize the covariates in the pharmacodynamic relationship between propofol Ce and adequate and deep sedation in patients undergoing spinal anaesthesia. Materials and MethodsStudy population. This study was approved by the ethics committee of the Yonsei University Health System (4...

Effect of baseline cognitive impairment on association between predicted propofol effect site concentration and Bispectral index or sedation score

“…This is consistent with Schnider et al [19] who observed increasing sensitivity to propofol in elderly patients for loss of consciousness. Both age and level of spinal anesthesia have been reported to modify sedation scores [28]. In the current study, age is the more important modifying factor of OAA/S as the overall level of spinal anesthesia demonstrated little variation among participants (T9 ± 1.5 dermatomes).…”

Impact of Chloroprocaine on the Eligibility for Hospital Discharge in Patients Requiring Ambulatory Surgery Under Spinal Anesthesia: An Observational Multicenter Prospective Study

“…Since spinal anesthesia can be a stressful experience, premedication was administered to some patients to facilitate their comfort during anesthesia performance. Therefore intraoperative sedation is a common practice [15,16]. After the spinal block procedure, the upper level of the sensory block was evaluated using the cold test, and motor blockade was assessed with a modified Bromage score [17].…”