Barbara Wyler

Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: performance of three pharmacokinetic–dynamic models

BACKGROUND In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce(PROP)), for any Ce(PROP), the corresponding hypnotic effect should be constant. We compared three PK-PD models (Marsh PK with Shüttler PD, Schnider PK with fixed ke0, and Schnider PK with Minto PD) in their ability to maintain a constant bispectral index (BIS), while using the respective effect-site-controlled target-controlled infusion (TCI) algorithms. METHODS We randomized 60 patients to Group M (Marshs model with k(e0)=0.26 min(-1)), Group S1 or Group S2 (Schniders model with a fixed k(e0)=0.456 min(-1) or a k(e0) adapted to a fixed time-to-peak effect=1.6 min, respectively). All patients received propofol at a constant rate until loss of consciousness. The corresponding Ce(PROP), as calculated by the respective models, was set as a target for effect-site-controlled TCI. We observed BIS for 20 min. We hypothesized that BIS remains constant, if Ce(PROP) remains constant over time. RESULTS All patients in Group M woke up, one in Group S1 and none in Group S2. In Groups S1 and S2, BIS remained constant after 11 min of constant Ce(PROP), at a more pronounced level of hypnotic drug effect than intended. CONCLUSIONS Targeting Ce(PROP) at which patients lose consciousness with effect-site-controlled TCI does not translate into an immediate constant effect.

Training to deeper compression depth reduces shallow compressions after six months in a manikin model.

INTRODUCTION Studies show that students, trained to perform compressions between 40 and 50mm deep, often do not achieve sufficient depth at retention testing. We hypothesized that training to achieve depths >50mm would decrease the proportion of students with depth <40mm after 6 months, compared to students trained to a depth interval of 40-50mm. METHODS A basic life support (BLS) self-learning station was attended by 190 third year medicine students. They were first offered the possibility to refresh their skills, following the instructions of a 15min abbreviated Mini Anne™ video (Laerdal, Norway) using a full size torso and a face shield. This was followed by further training using Resusci Anne Skills Station™ software (Laerdal, Norway). Voice feedback was provided according to randomisation to a standard group (SG) 40-50mm and a deeper group (DG) >50mm. Quality of compressions was tested after 6 months. RESULTS The SG and DG groups consisted of 90 (67% female) and 100 (58% female) participants respectively. At the end of training, all students reached the target depth without overlap between groups. After 6 months, the proportion of students achieving a depth <40mm was 26/89 (29%) in the SG vs. 12/89 (14%) in the DG (P=0.01). The proportion of students with a depth >50mm was 5/89 (6%) for the SG and 44/89 (49%) in the DG (P<0.001). CONCLUSIONS The educational strategy to train students to a deeper depth, reduced shallow compressions 6 months after training.

The response of bispectral index to laryngoscopy, comparison between hemispheres in patients with a brain tumour versus a healthy control group

Background and Goal of Study: Electroencephalogram during anaesthesia may be affected by brain tumour.(1) We studied whether patients with a brain tumour have different BIS responses after laryngoscopy (LAR). We compared tumour patients with healthy control patients. Materials and Methods: After EC approval, 40 ASA 1 or 2 patients (control) and 41 intracranial tumour patients(tumour) received standardized anaesthesia while measuring bilateral BIS (BIS VISTAXP4 with bilateral sensor).(Covidien, Dublin, Ireland) Remifentanil was randomized to 3 or 5ng/ml effect‐site concentration (Minto) and maintained throughout the study. Propofol effect‐site concentration(CePROP)(Schnider) was set at 2 μg/ml and increased with incremental steps of 0.5 μg/ml until loss of consciousness was observed. After 3 minutes, laryngoscopy was performed and BIS was monitored during one minute. The median BIS of 1 minute before LAR is subtracted from the median BIS one minute after LAR to obtain delta BIS for each hemisphere. We tested if delta BIS is significantly different between hemispheres in control, between healthy and diseased hemispheres in tumour and between ipsilateral control and tumour hemispheres. Statistical significance was set at p< 0.05. Results and Discussion: No demographic differences were present except for age.(table 1) Delta BIS is not statistically different, neither between hemispheres in control, nor between healthy and diseased hemispheres in tumour groups.(table 2) No significant difference was found in delta BIS between ipsilateral control and pathological hemispheres. Conclusion(s): Bilateral BIS does not provide additional information on responsiveness to a standardized stimulus. We could not observe major differences in bilateral BIS response between control and brain tumour patients. Unilateral BIS monitoring seems to be equally informative in healthy and brain tumour patients compared to bilateral monitoring.