University Department of Anaesthesia, Glasgow Royal Infirmary, 10 Alexandra Parade,Glasgow G31 2ER, UK
This research was presented in
part at the Annual Meeting of the American Society of Anesthesiologists,
Dallas, 1999.
Abstract
We investigated the safety of a patient-maintained system that allows individuals to operate a target-controlled infusion of propofol to achieve sedation. Ten healthy volunteers were recruited and instructed to try to anaesthetize themselves with the system. A target-controlled infusion of propofol was set to deliver a target propofol concentration of 1 µg ml1, and the subjects allowed to increase the target in increments of 0.2 µg ml1 by pressing a control button twice in 1 s. There was a lockout time of 2 min and a maximum permitted target concentration of 3 µg ml1. Heart rate and pulse oximetry oxygen saturation (SpO2) were monitored continuously, and non-invasive arterial pressure, ventilatory frequencies and sedation scores were measured every 5 min. Sedation was continued until the subject stopped pressing the button. A keyword was then read for the individual to remember and sedation discontinued. There were no instances of significant decrease of SpO2 or loss of airway control. Maximum target blood concentration of propofol recorded ranged from 1.4 to 3 µg ml1. Two subjects became oversedated, one of whom was unrousable with loss of eyelash reflex. No subject could recall the keyword, although one recognized it from a list of 10 words. We conclude that the patient-maintained sedation system described could not be guaranteed to produce only conscious sedation in all patients, and that close clinical supervision by an anaesthetist would still be required for safe operation.
Br J Anaesth 2000; 85: 299301
Keywords: anaesthesia; anaesthetics i.v., propofol; sedation; patient-controlled
Patient-controlled sedation systems, which administer bolus doses of the agent, have been studied by other investigators and found to be both an effective1 and popular2 technique for patients undergoing surgery under regional anaesthesia. A patient-maintained sedation system, which delivers a target-controlled infusion of propofol, has also been used successfully to provide sedation for patients undergoing orthopaedic surgery,3 and more recently as an anxiolytic premedication for patients undergoing day surgery.4 With any system in which the patient has control of sedative administration, a major concern is safety, as regards the depth of sedation that can be achieved and the maintenance of cardiorespiratory function. The goal of any patient-controlled sedation system should be delivery of conscious sedation while operating safely to prevent oversedation. Ultimately this safety depends on the appropriateness of the staged increase in dose of the sedative drug, the effectiveness of the lockout interval in allowing equilibration of the drug with the effect site, and the ability of the subject to coordinate a successful push of the control button. These three elements should function together in a feedback loop to prevent oversedation in all situations, including that in which individuals might be determined to administer as much sedative as possible through repetitive operation of the control button. We aimed to test the feedback loop of our system, in such a situation, in healthy volunteers who were asked to operate the system repetitively in an attempt to anaesthetize themselves.
Methods and results
Local Ethics Committee approval for the study and written informed consent were obtained from 10 healthy adult volunteers, aged 1840 yr. The exclusion criteria were a history of intercurrent disease, cardiorespiratory, renal or hepatic dysfunction, psychiatric disorder or mental retardation, use of any medication with sedative effects or a history of anaesthetic problems. The experimental target-controlled infusion (TCI) system used for sedation consisted of a Graseby 3400 infusion pump, the rate of which was controlled by a backbar microprocessor programmed with pharmacokinetic data describing the distribution and elimination of propofol.5 By entering the subjects age and weight, and the desired initial blood concentration of propofol, the system calculates the initial bolus and variable infusion rates to achieve and maintain this concentration as given by the pharmacokinetic model, and gives a calculated figure for effect site concentration.6 Connection of a control button to the backbar enables the subject to increase the target blood concentration (CT) of propofol in increments of 0.2 µg ml1 by double pressing the button within 1 s. There is then a lockout period of 2 min during which no further increase is possible with a maximum attainable target concentration of 3 µg ml1. If no successful presses are detected for a period of 6 min, there is a stepped reduction in the target concentration to a minimum of 0.2 µg ml1.3 4
Before starting the sedation, the subjects were instructed in the use of the control button and allowed to get the feel of its operation. They were instructed to press the button as often as they could in an attempt to anaesthetize themselves. Measurement of non-invasive arterial pressure (NIBP), heart rate (HR), ventilatory frequency and pulse oximetry oxygen saturation (SpO2) were recorded, and a 21G intravenous cannula sited. A target-controlled intravenous infusion of propofol (1% with lignocaine 20 mg per 50 ml) was started at an initial target concentration of 1 µg ml1, and time allowed for the calculated effect site concentration, as determined and displayed by the system,6 to reach within 0.1 µg ml1 of the set blood target level. The control button was then activated and the subject reminded to double press it as often as possible. One further verbal encouragement to push the button was given during the study period if they failed to push it for more than 3 min.
Heart rate and SpO2 were monitored continuously, NIBP, ventilatory frequency and sedation score, using a modified Steward sedation score,3 were measured every 5 min following the start of sedation. Sedation scores were assessed by one of the two authors, who were familiar with the assessment and scoring of sedation levels. Oversedation was defined as loss of response to verbal command. An SpO2 <94% or ventilatory frequency <8 were considered clinically significant and were to be treated with supplementary oxygen. A decrease in baseline NIBP or HR >30% or HR <50 min1were to be treated as considered appropriate by the investigator.
Any sign of anaesthesia, such as loss of verbal contact or loss of eyelash reflex, was recorded. Sedation was discontinued if the subject became unresponsive or failed to double press the control button on three attempts or for a period of more than 3 min, if there was loss of airway control, pulse oximetry oxygen desaturation below 94% on room air, or the target concentration reached the maximum level of 3 µg ml1. This was the primary end point at which the deepest level of sedation achieved, the greatest predicted blood and corresponding effect site concentration of propofol reached were recorded. At this time a keyword was read for the subject to remember. One hour after discontinuing the sedation, subjects were asked to repeat the keyword. If unable to do so a list of 10 words including the keyword was read out and again the subject was asked to identify it.
Ten healthy volunteers were recruited to the study. Subject characteristics are shown in Table 1. Maximum Steward sedation scores ranged from 2 to 8 with a median of 5, scores for consciousness, airway and activity at the maximum CT propofol reached are shown in Table 1. Maximum CTpropofol reached ranged from 1.4 to 3.0 µg ml1 with a median of 2 µg ml1. The total dose of propofol administered ranged from 105 to 351 mg.
|
No subject had automatic recall of the keyword, although one, whose lowest score for consciousness score was 3 at the maximum CT propofol of 3 µg ml1, recognized it when it was read from the list.
Comment
Our system functioned to prevent oversedation in 80% of the subjects studied, all of whom were actively trying to anaesthetize themselves. For these individuals the feedback loop provided by the patient control button functioned well. The need to double press the button appeared to be an important safety factor for three individuals who could not coordinate a double press at maximum sedation level. However, two subjects became oversedated, with one displaying signs of anaesthesia. It is possible that our increments of CT propofol 0.2 µg ml1 and 2-min lockout time failed to provide an adequate feedback loop. Reducing the staged increments in target concentration, and so delivery dose, with each successful press and increasing lockout time could allow more complete equilibration of blood and effect site concentrations of propofol and, therefore, could reduce the incidence of oversedation.
Thorpe and colleagues7 studied 100 patients who were asked to anaesthetize themselves with a system delivering boluses of propofol with no lockout period. They reported an 11% incidence of oversedation with 2% reaching unresponsiveness. The total doses of propofol that their patients self-administered varied over a fourfold range from 66 mg to 248 mg. The twofold range of maximum target concentrations reached by our volunteers is likely to be a combination of the error inherent in estimates of predicted blood propofol levels (pharmacokinetic variability) and the predictable variability in pharmacodynamic response to propofol, reinforcing the need for careful titration of sedation according to individual needs. This variability makes it difficult to design a foolproof system to prevent oversedation.
For our subjects the motivation to press the control button relied entirely on the initial instruction given and one reinforcement on their first failure. This repeat instruction was given in an attempt to mirror the clinical situation where individuals will respond to heightened stimulation by pressing the control button. However, for ethical reasons, it is clearly difficult to recreate such surgical conditions and we acknowledge that our subjects were not exposed to any real clinical stimulation.
It is interesting that none of the volunteers had spontaneous recall of keywords, indicating that all had reached an amnesic level of sedation. Implicit memory could account for the recognition of the keyword by one volunteer, although this could equally be a chance finding.
In conclusion, the fact that two individuals became oversedated, with one showing signs of anaesthesia, indicates that, in its existing form, the patient-maintained sedation system described could be not guaranteed to produce conscious sedation in 100% of subjects instructed to attempt to anaesthetize themselves. How accurately this would reflect real clinical use may be debated, but we must conclude that close clinical supervision by an anaesthetist would be required to operate this system safely. However, the blood concentration of propofol decreases rapidly when the drug infusion is discontinued which would allow rapid recovery to a state of conscious sedation for those individuals who were oversedated. Further investigations looking at the effects of altering incremental doses and lockout times on improvement of the feedback loop are warranted.
Footnotes
* Corresponding author:
Department of Anesthesiology, Duke University Medical Center, Box 3094,
Durham, North Carolina 27710, USA
References
1 Grattidge P. Patient-controlled sedation using propofol in day surgery. Anaesthesia 1992; 47: 68385[ISI][Medline]
2 Osborne GA, Rudkin GE, Jarvis DA, Young IG, Barlow J, Leppard PI. Intra-operative patient-controlled sedation and patient attitude to control. A crossover comparison of patient preference for patient-controlled propofol and propofol by continuous infusion. Anaesthesia 1994; 49: 28792[ISI][Medline]
3 Irwin MG, Thompson N, Kenny GN. Patient maintained propofol sedation. Assessment of a target-controlled infusion system. Anaesthesia 1997; 52: 52530[ISI][Medline]
4 Murdoch JAC, Kenny GNC. Patient-maintained propofol sedation as premedication in day-case surgery: assessment of a target-controlled system. Br J Anaesth 1999; 82: 42931
5 White M, Kenny GN. Intravenous propofol anaesthesia using a computerised infusion system. Anaesthesia 1990; 45: 2049[ISI][Medline]
6 White M, Schenkels MJ, Engbers FH, Vletter AA, Burm AG, Bovill JG, Kenny GN. Effect-site modelling of propofol using auditory evoked potentials. Br J Anaesth 1999; 82: 3339
7 Thorpe SJ, Balakrishnan VR, Cook LB. The safety of patient-controlled sedation. Anaesthesia 1997; 52: 114450[ISI][Medline]