Effect site targeted patient-maintained sedation with propofol
AR Absalom*, FHM Engbers#,
N Sutcliffe*, GNC Kenny*
*University Department of Anaesthesia, Glasgow Royal Infirmary,
Glasgow, Scotland
#Department of Anesthesiology, Leiden University Medical Centre,
Leiden, The Netherlands
Background: Early patient-controlled sedation systems administered boluses or
continuous infusions of sedative drugs on patient demand [1,2]. More recently
Kenny and colleagues have developed a patient-maintained sedation system based
on a target-controlled infusion (TCI) of propofol [3]. With this system a demand by the patient increases the target
blood concentration of propofol by a fixed amount. However, unless the lockout
period is very long, the blood propofol concentration can get far ahead of the
brain concentration. If this happens the brain concentration may continue
rising after the patient has stopped pressing the button, and this may render
the patient unresponsive or unconscious. A TCI system that targets the
effect-site (brain) concentration may enhance safety by overcoming this
problem.
Methods: We have studied the safety of such a system in 9 healthy adult
volunteers. The Bispectral Index was measured and recorded continuously
throughout the study period. Baseline physiologic measurements (heart rate,
blood pressure, SaO2) were made before starting, and thereafter every 5
minutes. Subjects were asked to press the handset as often as they wished, with
the aim of trying to render themselves unconscious. When the handset button is
pressed the system increases the propofol target by 100mcg/ml. It administers a
bolus of propofol to rapidly increase the blood concentration to a level above
that of the desired brain concentration. This is followed by an infusion, but
the system then allows the blood concentration to decrease until the brain and
blood concentrations converge on the new target concentration. The lockout
period is 60 seconds. Sedation score, BIS, and the target and estimated brain
and blood concentrations were recorded every minute. Once the subject stopped
using the handset the target was set to zero, and the subject observed until
fully recovered.
Results: Six male and 3 female subjects were enrolled. Verbal contact was
maintained with all subjects throughout the study. The median brain
concentration at which subjects stopped using the handset was 2.2mcg/ml (range
1.3 to 3.9mcg/ml). At this point the median BIS was 66 (range 53 to 80). No
subject was able to render him/herself unconscious. Physiological variables
were stable throughout. There were no episodes of oxygen de-saturation, no
subjects required supplementary oxygen, and there were no adverse effects other
than aching in the arm during rapid infusion of propofol.
Conclusion: In the subjects we have studied, effect site targeted
patient-maintained propofol sedation has provided effective sedation that was
pleasant, free of serious adverse effects and safe.
1. Rudkin G et al. Intra-operative
patient-controlled sedation. Anaesthesia 1992; 47: 376-81.
2. Osborne GA et al. Intra-operative
patient-controlled sedation and patient attitude to control. Anaesthesia 1994; 49:
287-92.
3. Irwin MG et
al. Patient maintained propofol sedation. Assessment of a target-controlled
infusion system. Anaesthesia 1997; 52: 525-30.