A prospective observational study of effect-site targeted, patient-maintained propofol sedation for lower limb orthopaedic surgery performed under spinal anaesthesia

Editor, Many patients experience anxiety when undergoing awake procedures.1 Procedural anxiety is an intrinsically negative experience and is associated with deleterious surgical outcomes such as postoperative pain.2 Target-controlled infusion of propofol is a popular choice for intra-operative sedation because of the drug's favourable pharmacokinetic profile. However, anaesthetists have been shown to be inaccurate in judging patients’ pre-operative anxiety.3 This could result in insufficient or excessive dosing of sedation in relation to the actual anxiolytic requirements of individual patients. One possibility for overcoming this is allowing patients to exert control over the depth of their sedation. The aim of this study was to examine the ability of patients to sedate themselves using effect-site targeted (Cet), patient-maintained propofol sedation (PMPS) under the supervision of an anaesthetist in lower limb orthopaedic surgery performed under spinal anaesthesia. Ethical approval for this study was provided by NHS Research Ethics Committee Wales 6 (Reference: 16/WA/0080) on 17 March 2016. The study was registered on Research Registry (Reference: 2521). We obtained written consent from all individuals. Reviews of previously published studies suggested that a convenience sample of 25 patients would provide useful data regarding the technique. Inclusion criteria were age more than 18 years presenting for elective lower limb orthopaedic surgery, expressing a pre-operative preference for surgery to be performed under regional anaesthesia with sedation. Exclusion criteria were inability to use a hand-held button, need for surgery to be conducted under general anaesthesia, contraindication to the use of propofol and inability to communicate in English. After establishing routine monitoring and intravenous access, a spinal anaesthetic using 12 to 15 mg of hyperbaric bupivacaine was performed. After confirming sensory block to T10, we commenced a Cet PMPS regimen using Schnider modelling4 (Alaris PK; Carefusion, Basingstoke, UK). We gave patients a hand-held button indicating a request for deepening of sedation. We asked individuals to ‘press the button if you feel anxious or want to be more sleepy’. On hearing a beep indicating a button-press, a study investigator adjusted the Cet according to a standardised protocol. We commenced the Cet at 0.5 μg ml−1 and incremented this by 0.2 μg ml−1 up to a maximum of 2.0 μg ml−1. We ignored repeat button-presses until the calculated effect-site concentration was equal to the target. If patients did not press the button for 6 min, we reduced the Cet by 0.1 μg ml−1. At the end of surgery, we discontinued the sedation and transferred patients to the postanaesthetic care unit, recording the time taken to achieve a modified Aldrete Score at least 9. We administered a postoperative questionnaire seeking feedback on the use of the sedation system and general narrative responses. Twenty-six patients received PMPS between 26 May 2016 and 22 March 2017. There were no instances of adverse physiological disturbance (>20% deviation from baseline before spinal anaesthesia), airway compromise or apnoea during the sedation. The median (interquartile range, IQR [range]) modified Wilson sedation score during surgery for all patients was 2 (1 [1 to 4]). The mean (SD) calculated effect-site concentration during surgery for all patients was 0.73 (0.32) μg ml−1, and the mean (SD) maximum calculated effect-site concentration was 0.89 (0.48) μg ml−1. Fourteen patients used the button a median (IQR [range]) of 6 (6 [1 to 29]) times; the remaining 12 patients chose not to press the button. Median (IQR [range]) time to Aldrete Score at least 9 was 6 (14 [1 to 58]) min. Figure 1 shows patients were able to alter their depth of sedation according to personal preference. There was a positive correlation (ρ = 0.76) between calculated effect-site concentration of propofol and depth of sedation measured using the modified Wilson Sedation Scale.Fig. 1: Calculated effect-site concentration of propofol during sedation for four patients. Patient 1 (dotted line), patient 2 (solid line), patient 3 (dashed line), patient 4 (double line).Patient 1 appeared anxious pre-operatively and chose to achieve a deep level of sedation as soon as the button was provided. Patient 2 initially chose not to press the button, but when surgery commenced, with associated noise, decided to deepen the sedation. Patient 3 used the button intermittently throughout the procedure and maintained a steady depth of sedation. Patient 4 appeared relaxed for most of surgery and did not press the button until the noisy siting of the knee prosthesis, at which point the sedation was deepened. Narrative responses on the sedation regime included ‘it was comforting to know that you could do it if you wanted to’ and ‘although I didn’t use the button I liked knowing that I could have if I had wanted to’. There were no negative narrative responses. When asked whether they felt they were sedated to the right level, 25 out of 26 patients recorded: ‘I felt I was sedated at the right level’. One patient recorded: ‘I cannot remember’. Median (IQR [range]) 10-point numeric rating scale response was 10 (1.4 [5 to 10]) for satisfaction with sedation. When asked if they would use the same sedation technique again, 25 out of 26 patients responded with ‘very likely’ or ‘likely’, one patient responded ‘unsure’. By applying PMPS in the setting of spinal anaesthesia, we have shown that the technique is useful wherein the hypnotic-anxiolytic properties of propofol can be tailored to the anxiety of individual patients in a procedure associated with no intra-operative pain. Our study suggests that an upper limit of 2.0 μg ml−1 in nonpainful procedures is sufficient for the purposes of anxiolysis. Our study replicates the previous findings of high levels of satisfaction with PMPS.5,6 The narrative responses from patients also suggest a degree of empowerment felt by holding a control button. Further studies should address the extent to which this feeling of empowerment translates into reduced procedural anxiety. Conclusions drawn from data arising from observational trials on the safety and utility of anaesthetic techniques must be interpreted carefully.7 Although our work reports no incidences of physiological compromise, a much larger sample size is required to provide evidence regarding the safety of this technique. We have, however, demonstrated that PMPS can deliver individualised procedural sedation for patients presenting for elective lower-limb orthopaedic surgery under spinal anaesthesia with a high degree of patient satisfaction. Future research should develop and obtain regulatory approvals for the investigation of fully automated systems capable of patient-maintained propofol sedation. Acknowledgements relating to this article Assistance with the study: we are grateful to the Research Nurses of the Department of Research and Education (Critical Care, Acute Medicine and Emergency Department), Nottingham University Hospitals NHS Trust, for their efforts during data collection. Financial support: this study was supported by a research grant from B.Braun Melsungen AG. B. Braun Mesungen AG has no role in the study design, data collection, data analysis, decision to publish or preparation of the manuscript. Conflicts of interest: none.