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Keywords:

  • Anaesthetics;
  • intravenous;
  • propofol

Summary

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. References

In this study, we evaluated safety and recovery using a patient maintained, target controlled infusion of propofol for sedation in 20 patients undergoing colonoscopy. Using a handset with a two-minute lockout interval, patients could make 0.2 µg.ml−1 increments to an initial target plasma concentration of 1 µg.ml−1 up to a maximum 4.5 µg.ml−1. Four patients became oversedated but required no airway or circulatory interventions. Subjects had a significant reduction in mean (SD) heart rate: 78.7 (15) vs. 69.8 (13.5) (p < 0.001) and in systolic blood pressure 121.1 (13.2) mmHg vs. 96.5 (8.6) mmHg (p < 0.001). Choice reaction time testing 15 min after colonoscopy showed a significant median (IQR [range]) rise of 162 (− 16, 383.3 [-199–859]) ms (p < 0.05). Six patients had faster reaction times postcolonoscopy. All patients denied unpleasant recall and were satisfied with the system. Although oversedation was a problem in this model, we conclude that patient maintained propofol sedation could be possible for colonoscopy.

A recent report by an intercollegiate working party, chaired by the Royal College of Anaesthetists [1] reviewed the evidence for the provision of safe sedation and found that sedation practices were often still suboptimal. This was despite adequate safety guidelines being available in the literature. Improvements in the safety of sedation techniques are clearly still required and in this study we examined the safety aspects of a novel patient maintained sedation system for use during colonoscopy, which may have some advantages over traditional methods.

Colonoscopic examinations are usually carried out in an outpatient setting and there are implications for the use of sedation in outpatients. Firstly, complication rates for endoscopic procedures are increased by the use of opiate/benzodiazipine sedation [2–9]. The most common adverse events encountered are cardiovascular complications or respiratory depression [10–12]. This is particularly the case in the elderly or less fit [12–14]. Secondly, there may be resource and cost implications, as post sedation recovery time is required. In addition, patients are usually advised not to return to work or drive following sedation and a second adult may be required to accompany the patient home. Patient satisfaction with sedation is another area where current practice may be suboptimal [15–18]. Improvements in quality, safety and recovery time from sedation would therefore seem desirable goals and formed the basis for this study.

The trend most often in colonoscopic practice is for sedation to be given [2, 10, 12, 19], although, some studies have confirmed the feasibility and acceptability of colonoscopy in the absence of sedative medication [3–9]. The most common drugs used for sedation are benzodiazipines, such as midazolam, used either alone or with the addition of an opioid such as pethidine [2, 10, 12]. An alternative sedative drug is propofol. Target controlled infusion (TCI) [20] is a mode of drug delivery used in anaesthetic practice to administer a preset target blood propofol concentration. This system can be adapted to allow patient maintained sedation (PMS) by the inclusion of a handset. Such PMS systems have been used already with little oversedation, few cardiovascular effects and high patient satisfaction in volunteers [21], as sedative premedication for day surgery [22] and for patients having surgery under regional blockade [23]. The system has also been used successfully in patients undergoing ERCP [24].

There are theoretical benefits of a PMS system for patients undergoing colonoscopy. Patient control can allow tailoring of sedative drug to individual sensitivity, to the degree of stimulation present and to patient preference. In addition, the shorter duration of drug action seen with propofol might speed recovery following colonoscopy. Our primary aims in this study therefore, were to examine the safety and efficacy of a PMS system used during colonoscopy and to evaluate recovery by measuring patient reaction times. Patient satisfaction was also assessed using a questionnaire.

Methods

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. References

Following local ethics committee approval, all patients attending for colonoscopy and considered fit for sedation were eligible for inclusion in the study. Exclusion criteria included inability to physically use the handset or to comprehend the instructions for its use.

Written, informed consent was obtained from 21 patients who agreed to participate in this pilot study. Study patients all completed a computerised reaction test [25] prior to administration of any sedative drugs. The choice reaction time (CRT) test requires subjects to watch a computer screen where a series of numbers appear periodically. As each number appears the patient must move their finger from the spacebar to the corresponding number on the keyboard then back to rest on the spacebar. The time in milliseconds taken from the number appearing on screen to the subject selecting a key corresponding to that number is the total CRT. The number of errors made is also recorded.

Having completed the reaction test, baseline observations of pulse, saturation and blood pressure were made prior to sedation being commenced. ECG and saturation monitoring continued throughout the sedation and recovery period and blood pressure was recorded at 10-min intervals. Supplemental oxygen was given to all patients via nasal cannulae at 2 l min−1.

Propofol was administered through an intravenous cannula using a modified TCI system. The system comprises a Graseby (Watford, Herts, UK) 3400 infusion pump, controlled by a back bar microprocessor system. The microprocessor is programmed with the pharmacokinetic data [26] describing the distribution and elimination of propofol, which is also used in the Diprifusor module of modern TCI infusion devices. The operator enters the patient age and weight into the microprocessor and the system displays the target blood concentration and the calculated effect site (brain) concentration. The modification of the TCI system comprised a handset attached to the back bar, held by the patient who presses it to increase the target blood concentration. In this study a double press of the handset button increased the target concentration by 0.2 µg.ml−1. The machine had a lockout period of 2 min during which time no increase in the target concentration is possible. The maximum target concentration possible was set at 4.5 µg.ml−1. In addition, the investigator had the ability to manually override the system to alter the concentration in the event of over or undersedation.

The patients were given an initial target value of 1 µg.ml−1 loading dose then allowed to sedate themselves using the handset for a period of approximately 20 min prior to commencing the colonoscopy. They were encouraged during the procedure ‘to press the button if they wanted to be more sleepy’. Sedation scores using a scoring system (Table 1) were recorded at 10 min intervals throughout the sedation period and every 5 min during the recovery period. Anaesthetic interventions were documented.

Table 1.  Sedation Scoring System.
Level of SedationScore
Awake and anxious1
Awake and not anxious2
Speech slurred3
Eyes closed responds to speech4
Eyes closed responds to shaking5
Unresponsive6

At a period of 15 min following discontinuation of the propofol infusion the patient was asked to repeat the choice reaction test. Later, after return to the day case ward the patients were asked to complete a questionnaire to assess recall and satisfaction.

Parametric data were analysed using the paired t-test and non-parametric data were analysed with the Wilcoxon Rank Sum test.

Results

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. References

Of the 21 patients recruited into the study one patient, who had a history of a mild cognitive impairment secondary to a hypoxic brain injury at birth, was excluded. This was due to his subsequent refusal to allow monitoring or to complete the CRT test in the postoperative period. Table 2 summarises the characteristics and procedure details for the remaining 20 patients in the group.

Table 2.  Patient Characteristics and Procedure Information.
Number of patients20
  1. *Mean (SD).

Gender
 Male 9 (45%)
 Female11 (55%)
ASA status
 1 9 (45%)
 210 (50%)
 3 1 (5%)
Age (year)*53.6 (10.2)
Weight (kg)*69.3 (14.3)
Time sedated (min)*49.1 (9.3)
Scope duration (min)*16.3 (7.4)

Colonoscopic examination to the caecum was successfully completed in all patients. Seven of the patients required manual override of the PMS system by the investigator to adjust their level of sedation but no interventions were required for cardiovascular or airway compromise during the procedure. Four of the manual alterations in TCI level were decrements to correct perceived over sedation (sedation level > 5) and three were to increase sedation. All patients maintained an oxygen saturation > 94% throughout the period of monitoring and although one patient vomited during the procedure this resulted in no airway soiling.

Compared to pre sedation measurements, there was a significant decrease in mean (SD) heart rate 78.7 (15) vs. 69.8 (13.5) (p < 0.001, 95% CI 4.47, 13.03) beat.min−1 and systolic blood pressure 121.1 (13.2) vs. 96.5 (8.6) (p < 0.001 95% CI 18.8, 30.3) mmHg.

The median (IQR [range]) maximum target propofol level during the sedation period was 2.7 µg ml−1 (2.4, 3.0[2–3.4]) (Fig. 2) and sedation score level was three or higher in all patients whilst the colonoscopy was carried out. Fifteen min after colonoscopy all patients had a sedation score of three or less and all were able to complete the CRT test. Comparison of pre and post sedation total CRT test results showed a statistically significant prolongation in total CRT post colonoscopy. The median (IQR [range]) total rise in CRT was 162 (−16, 383.3 [−199–859]) ms (p < 0.05 95% CI 50, 343). The subjects made a total of eight errors overall, in number selection, five were made in the presedation period and three after sedation was discontinued. Of note six patients had a faster total CRT following sedation.

image

Figure 2. Median TCI Propofol levels during Study Period.

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A postoperative questionnaire, given to patients in the recovery period, confirmed overall patient satisfaction and low rate of recall. All patients were satisfied with the technique and were prepared to have the same sedative in the future. Only two patients had any recall at all of the procedure and this was rated as ‘not unpleasant’. Only one patient made negative comment, which was related to mild discomfort in the arm caused by the infusion.

Discussion

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. References

We have assessed a PMS system for colonoscopy and demonstrated it has significant but mild effects on cardiovascular parameters, is associated with rapid recovery and is popular with patients. In its current form however, problems with oversedation exist.

Although in this study, statistically significant haemodynamic changes in pulse and systolic blood pressure are documented, the actual clinical significance of these is debatable. In no case was treatment or intervention required. It has been noted in previous studies that changes in heart rate and blood pressure occur during colonoscopy with other forms of sedation and indeed, may also occur when no sedation at all is used [3, 27–30]. In this study the reduction in heart rate was seen more commonly either during or after colonoscopy. The lowest pulse rate recorded in any patient was 46 beat.min−1 and that patient had a low baseline pulse rate of 50. It is likely therefore that the reduction in heart rate we measured reflects reduction in level of anxiety and stimulation by the sedation rather than any true vagal response to the colonoscopy itself.

Reduction in blood pressure occurred immediately prior to or at the start of colonoscopy. Propofol is known to have mild cardio-depressant and vasodilatory effects, which could be responsible for this observation. In addition, the patients in this study, having had colonic preparation, may be mildly dehydrated which would tend to exaggerate these effects on blood pressure. Although, as with heart rate reduction, no patient required treatment and the blood pressure normalised in the course of the procedure or during recovery, it may be that, for patients with cardiovascular disease, caution using the system should be recommended. The patients in this study were a relatively young and fit group (Table 2). Hypotension may be more problematic in elderly patients or less fit patients so this method of sedation cannot be currently recommended in those groups. However, it should be noted that other studies have documented hypotension following midazolam sedation for endoscopy [31, 32] so the PMS system may be no worse than sedation methods already in use for these groups.

The mean upper limit target concentration used by patients for this procedure was 2.7 (range 2.0–3.4) µg.ml−1, which is higher that that seen in previous studies looking at the use of the system for premedication [22] and sedation during regional anaesthesia [23]. However, studies of its use in ERCP [24] have required similar doses, demonstrating that, unsurprisingly, the requirement for sedation is higher during more stimulating procedures.

The need to override patient control was high in this study compared with previous studies. In the cases of undersedated patients (n = 3) this appeared to be secondary to patient difficulty in double pressing the handset activation button. Although the double press was originally included as an additional safety feature, it may be that during colonoscopy patients desire to be more sleepy and in these circumstances co-ordination of a double press appears to be too complicated and single press may be more appropriate. The system is currently being evaluated in another study of patients having ERCP using single press activation.

Four patients in the study became oversedated, underlining the importance of supervision of any sedated patient by an individual other than the colonoscopist. A major benefit of the PMS system however, is that in the event of oversedation, drug offset is very swift and sedation can be very quickly lightened or terminated using the override facility. The high incidence of oversedation does however, indicate that the current increment and lockout interval may not provide an adequate safety feedback loop and a reduction in handset TCI increments or an increase in the lockout interval should be evaluated to address this oversedation problem in future trials.

Not surprisingly, impairment of psychomotor function was seen 15 min following discontinuation of the infusion of propofol with a mean total rise in CRT of 162 ms. This compares favourably to post sedation CRT after morphine and midazolam where Hay [33] found a rise of 517 ms in CRT was still present even after 2 h. As an index for comparison, in a previous study, Grant [34] found a 118 ms rise in CRT at the legal limit of alcohol for driving a car in the United Kingdom (80 mg.100 ml−1). Clearly, the rise in CRT documented in this study with propofol constitutes a considerable improvement over conventional forms of sedation with implications of reduced patient recovery time and therefore possible cost savings.

Patient satisfaction is an important consideration when sedation is provided for colonoscopic procedures. The questionnaire given to patients in this study confirms that the PMS system is popular. This may be related to an increased feeling of control as seen with patient controlled analgesia with the added benefit of being able to self administer increments during the procedure. Another important factor contributing to satisfaction is the lack of unpleasant recall. In endoscopic practice the trend has been towards using lower doses of benzodiazipine to improve safety, however, these lower doses may be associated with higher incidence of patient recall of up to 70% with doses of 35 µg.kg−1 of midazolam [31]. Reduced patient willingness to return for repeat examination due to unpleasant experience undermines the potential benefits of colonoscopy as a screening procedure illustrating the potential importance of ensuring high patient satisfaction.

A disadvantage of the current system is the time taken for the patients to self-sedate. Although this was not formally measured the clinical impression was that 15–20 min should be allowed for the process. As higher mean plasma levels of drug are clearly required by patients having colonoscopy, compared with sedation in non- stimulating situations, it may be possible to increase the initial target concentration above 1 µg.ml−1, particularly in this group of relatively young fit patients. Another possible method of speeding up the self-sedation time is by using effect site targeting [35]. Systems developed in the future may be designed to target the estimated effect site (brain) concentration of propofol rather than the blood concentration therefore speeding onset of clinical drug action.

In conclusion, the results of this study suggest that colonoscopy can be carried out using a PMS system. The system is well tolerated by patients and results in minimal recall and a high degree of patient satisfaction. The incidence of oversedation found in our study would suggest that modifications are required to the system. Further research is required prior to recommending its use during colonoscopy.

References

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. References
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