Increasingly procedures which were once undertaken at open operation can now be achieved by less invasive means. Many procedures, which required a GA in the past, can now be performed under local anaesthesia and sedation. This has lead to an increase in the requirement for conscious sedation, for such procedures.
Traditionally physicians will administer intravenous boluses of hypnotic agent titrated to the point at which the physician thinks that the patient is "adequately sedated". Often combinations of opiate and hypnotic agents are employed for procedures associated with noxious stimuli not easily ameliorated by local anaesthesia. The aim of this technique is to produce a state of calm in a patient who is comfortable and maintaining his or her own airway, who may sleep but will be easily roused by command.
Unfortunately such a state is not easily achieved and maintained in a circumstance of variable surgical stimulus. Firstly the therapeutic window for acceptable sedation is narrow when compared to anaesthesia particularly using drugs with a delayed time to peak effect such as midazolam. It is all too easy to over-sedate a patient in an effort to achieve sedation within a reasonable time frame. This may lead to loss of airway and in an inadequately monitored and supervised situation may result in death. Further the wide pharmacodynamic variation between patients make it impossible to predict an appropriate dose for each individual patient.
Such difficulties have led a number of researchers to consider the use of patient controlled sedation (PCS). This technique involves the patient self administering the sedative agent to the point at which he or she is satisfied with the level of sedation. Such an approach has the potential to overcome the pharmacodynamic differences between individual patients
Over the past decade 30 studies of patient controlled sedation have been published of these 9 have been for procedures not requiring regional anaesthesia such as colonoscopy, or have been concerned with pre-operative anxiolysis. This leaves 21 studies of patient controlled sedation combined with locoregional anaesthesia. Most commonly midazolam and propofol have been the agents used either alone or in combination with opioids. The majority of these studies have used equipment designed for patient controlled analgesia delivering a bolus of drug in response to a button press by the patient. Bolus doses of propofol have been as low as 3mg and up to 0.7mg/kg for an adult patient with lock out times of between 0 and 3 minutes, Boluses of midazolam have ranged from 0.1 to 1.5 mg with lockouts between 0 and 1 minute. The choice of bolus dose and lockout period is a balance between speed of onset and safety. The larger the dose and shorter the lockout the faster the onset of sedation, and the more likelihood of over-sedation.
Theoretically the pharmacokinetics of propofol make it a more
suitable agent than midazolam for PCS. Propofol has a shorter
T1/2 Keo than midazolam leading to a shorter onset of action,
its higher clearance also leads to a shorter duration of action.
Four studies have compared PCS propofol and PCS midazolam. These
studies demonstrated a faster onset of sedation, less over-sedation
and better recovery in the propofol group. Rudkin and colleagues
compared midazolam PCS 0.5 mg bolus with propofol PCS 20 mg bolus
each with a 1 minute lockout period in patients having dental
procedures (1). There was good patient satisfaction with both
techniques, but propofol proved to be superior in terms of recovery
and rapidity on onset. The propofol group had a more favourable
ratio of successful to unsuccessful demands than the midazolam
group (8:3.2 and 14:19 respectively).
Eight studies have compared PCS with anaesthetist controlled sedation (ACS). In general drug usage and levels of sedation were lower and patient satisfaction higher in the PCS group. Osbourne and co-worker compared PCS propofol with ACS using an infusion of propofol in a randomised crossover study (2). There were no detectable differences between the groups in terms of recovery, operating conditions and total dose of propofol. However patients in the PCS group had lower sedation scores and expressed a stronger preference for the PCS technique. A further seven studies have combined opiate with the PCS as either a pre-medication, or as part of each PCS bolus. In general these groups had a higher incidence of nausea and respiratory complications but differences in PCS regimen and study design make direct comparison between studies difficult.
The limitation of standard bolus type PCS is that blood and effect site concentrations will never be stable. Each new bolus produces a peak concentration with the potential for over-sedation, the blood concentration then decays with time until a new bolus is initiated at which point the patient must be uncomfortable in order to initiate a new bolus. Kenny and colleagues have described a modified target controlled infusion (TCI) system that allows the patient to modify the set target concentration of propofol by using a push button. The term patient maintained sedation (PMA) has been used to describe this technique (3). The target concentration is increased by 0.2 *g/ml with each button press the new target being maintained thereafter. The system had a lockout period of 2 minutes to allow equilibration between blood and effect site concentration. Over the first 20 minutes if there were no button presses in any 6 min period the system automatically cut back the target by 0.2 *g/ml. From 20 minutes onwards the system decreased the target after 12 minutes without demand. Maximum permissible target was 3 ug/ml. This system was used to provide PCS for 36 patients undergoing surgery under locoregional anaesthesia an initial target of 1 ug/ml was selected by the anaesthetist and then control given to the patient. They reported good overall patient satisfaction and no over-sedation. Pain on injection was seen in 11% of patients, which is lower than many of the other studies.
All studies in this area describe satisfactory results with PSC and report a high degree of patient satisfaction. However all studies have involved supervision by an anaesthetist and few studies have reported any objectively measurable benefits. This begs the question does this technique represent an improvement over anaesthetist controlled sedation and can the delivery system be made safe enough to be used without anaesthetist supervision? Kenny and colleagues have used the PMA system in health volunteers asking the individuals to try to anaesthetise themselves. Out of 23 cases studied to date only one individual has become unresponsive during the sedation period but no airway intervention was required (4). We are currently using this system for PCS in patients undergoing joint replacement under regional anaesthesia.
A future development in this area would be the use of patient controlled effect site targeted infusion systems. Such an algorithm would allow rapid changes in the level of sedation without the risk of over-shooting the selected effect site target. We are currently assessing this technique in healthy volunteers.
References
1. Rudkin et al "Intra-operative patient controlled sedation"
Anaesthesia 1992,47:376-81
2. Osbourne et al "Intra-operative patient controlled sedation
and patient attitude to control" Anaesthesia 1994,49(4):287-92
3. Irwin et al "Patient maintained propofol sedation"
Anaesthesia 1997,52(6)525-30
4. Personal communication Professor GN Kenny Dept Anaesthetics
Glasgow University.