Reaction time-monitored patient-maintained propofol sedation: a pilot study in oral surgery patients.

Previous volunteer studies of an effect-site controlled patient-maintained sedation system using propofol have demonstrated a risk of oversedation. We have incorporated a reaction time monitor into the handset to add an individualised patient-feedback mechanism. This pilot study assessed if the reaction time-feedback modification would prove safe and effective in 20 healthy patients receiving sedation while undergoing oral surgery. All patients successfully sedated themselves without reaching any unsafe endpoints. All 20 maintained verbal contact throughout. The mean (SD) lowest peripheral blood oxygen saturation was 98.0 (2.1)% breathing room air. No patient required supplementary oxygen. The mean (SD) maximum effect-site propofol concentration reached was 1.6 (0.5) µg.ml(-1). The present system was found to be safe and effective, allowing oral surgery treatment under conscious sedation, but preventing oversedation.

The effect of propofol on patient reaction time and its relationship with loss of verbal contact before induction of anaesthesia.

Increasing the calculated plasma concentration of propofol has been shown to increase choice reaction time and visual and auditory response times. We studied the relationship of reaction to a vibrating handset as the effect-site target-controlled propofol concentration was incrementally increased in 20 patients during sedation, before induction of general anaesthesia. The reaction time increased, initially slowly and then more rapidly, as the calculated effect-site concentration of propofol increased, until the reaction to the vibrating handset was lost at a mean (SD) propofol effect-site concentration of 2.0 (0.6) µg.ml(-1) . The loss of response to verbal contact occurred at a propofol effect-site concentration of 2.4 (0.5) µg.ml(-1) . Reaction time may be of use clinically to warn of impending loss of verbal contact.

Patient-maintained propofol sedation using reaction time monitoring: a volunteer safety study.

Previous volunteer studies of an effect-site controlled, patient-maintained sedation system using propofol have demonstrated a risk of over-sedation. We have incorporated a reaction-time monitor into the handset of the patient-maintained sedation system to add an individualised patient-feedback mechanism. This study assessed if such reaction-time feedback modification would reduce the risk of over-sedation in 20 healthy volunteers deliberately attempting to over-administer themselves propofol. All the volunteers successfully sedated themselves without reaching any unsafe endpoints. All volunteers maintained verbal contact throughout, in accordance with the definition of conscious sedation. The mean (SD) lowest S(p) O(2) was 97 (1.7) % when breathing room air and no volunteer required supplementary oxygen. The mean (SD) maximum effect-site propofol concentration reached was 1.7 (0.4) µg.ml(-1) . The present system was found to be safer than its predecessors, allowing conscious sedation, but preventing over-sedation.

Evaluation of a new effect-site controlled, patient-maintained sedation system in dental patients.

We have designed a new effect-site controlled, patient-maintained sedation system for delivering propofol. In the previous systems we developed, the patients retained the use of the handset throughout the procedure and were able to increase the level of sedation. However, it was found that this could potentially lead to oversedation. In the present system, the patients were able to increase their level of sedation until a level was reached that was judged by the patients as being adequate to allow them to tolerate the injection of dental local anaesthetic. The handset was then taken from the patients and the effect site concentration of propofol was maintained at that level for the remainder of the procedure. To assess its safety and efficacy, the system was used to sedate 40 patients presenting for dental procedures under sedation. The system was used successfully and treatment was completed in 39 patients. The system was found to be safe. Both surgeon and patient approval scores were high. Although this study demonstrates the efficacy of effect-site controlled, patient-maintained propofol sedation in this group of patients, further work is required to confirm its safety.

Effect-site controlled patient maintained propofol sedation: a volunteer safety study.

Effect-site concentration is a mathematical term related to the clinical effect of a drug. We have designed a patient-maintained sedation system for delivering propofol to the predicted effect-site concentration rather than plasma concentration. To assess its efficacy and safety, 20 healthy volunteers deliberately attempted to over-sedate themselves using the system. The new effect-site concentration driven system delivered sedation successfully, and more rapidly than its predecessor. Fifteen volunteers ended the study when the system automatically reduced the effect-site concentration after 6 min of no button presses despite verbal contact and maintenance of arterial oxygen saturation (at effect-site concentration 1.8-3.8 microg x ml(-1)). Four out of 20 volunteers ended with minor arterial desaturation (lowest 88% at effect-site concentration 2.6-3.4 microg x ml(-1)). One volunteer ended after loss of verbal contact at effect-site concentration 3.4 microg x ml(-1). Further modification of the system's design is necessary before it can be recommended for routine practice.

A partially blinded randomised controlled trial of patient-maintained propofol sedation and operator controlled midazolam sedation in third molar extractions.

Patient-maintained sedation using propofol has recently been shown to be effective for dental surgery. We compared this new technique to the established technique of operator administered midazolam. The two groups were compared before, during and after sedation. The two primary outcomes were time until discharge and oxygen saturation. Vital signs, anxiety and psychomotor skills were also compared. State anxiety was reduced to a greater extent in the propofol group (mean difference 10 (SD 4) mm; p = 0.010. Propofol patients recovered quicker (mean difference 7 (SD 1.4) min; p = 0.001). Propofol patients had a smaller reduction in arterial oxygen saturation (mean difference 0.8 (SD 0.3)%; p = 0.030), and a reduced increase in heart rate (mean difference 9 (SD 2) beats.min(-1); p < 0.001). Both techniques were well tolerated and safe. Propofol sedation offered superior anxiolysis, quicker recovery, less amnesia and less depression of simple psychomotor function.

Patient maintained sedation for colonoscopy using a target controlled infusion of propofol.

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 micro g.ml(-1) increments to an initial target plasma concentration of 1 micro g.ml(-1) up to a maximum 4.5 micro g.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.

Accuracy of the 'Paedfusor' in children undergoing cardiac surgery or catheterization.

BACKGROUND: A prototype paediatric propofol target-controlled infusion (TCI) system, the 'Paedfusor' has been developed. This system incorporates a paediatric pharmacokinetic data set and algorithm specific for children in a Graseby 3500 anaesthesia syringe driver. In this study we have evaluated the accuracy of the Paedfusor TCI system in children who underwent either cardiac surgery or cardiac catheterization procedures. METHODS: Twenty-nine children aged 1-15 yr were investigated. General anaesthesia was provided using propofol administered by the Paedfusor system. Accuracy of the system was evaluated by obtaining up to 9 arterial samples for measurement of propofol concentration both during anaesthesia and in the recovery period. Measured arterial propofol concentrations were then compared with values calculated by the Paedfusor. RESULTS: The predictive indices of median performance error (MDPE), and median absolute performance error (MDAPE) of the Paedfusor system were found to be 4.1% and 9.7%, respectively and the median value for wobble was 8.3%. These values are much better than those found with the adult 'Diprifusor' system. CONCLUSION: The Paedfusor performance was found to be within the accepted limits for use as a TCI system.

Effect site concentrations of remifentanil and pupil response to noxious stimulation.

BACKGROUND: Opioid drugs block reflex pupillary dilatation in response to noxious stimulation. The relationship between the target effect site concentration (Ce(T)) of remifentanil and the pupil diameter and reactivity in response to a standard noxious stimulus were evaluated. METHODS: Anaesthesia was induced with propofol TCI to obtain loss of consciousness (LOC) in 12 ASA I/II patients. Thereafter, remifentanil Ce(T) was titrated by increments of 1 up to 5 ng ml(-1). In the awake state, at LOC and at each plateau level of remifentanil Ce(T), arterial pressure, heart rate, and BIS (A2000) were recorded. Pupil size and dilatation after a 100 Hz tetanic stimulation (T100) were measured at LOC and at each plateau level of remifentanil Ce(T). RESULTS: LOC was observed at a mean propofol Ce(T) of 3.53 (SD 0.43) microg ml(-1). Arterial pressure and heart rate decreased progressively from LOC to 5 ng ml(-1) remifentanil Ce(T) without any statistical difference between each incremental dose of remifentanil. Mean BIS values decreased from 96 (2) in the awake state, to 46 (12) at LOC (P<0.05) and then remained unchanged at all remifentanil Ce(T). Pupil dilatation in response to 100 Hz tetanic stimulation decreased progressively from 1.55 (0.72) to 0.01 (0.03) mm and was more sensitive than pupil diameter measured before and after 100 Hz tetanus. An inverse correlation between pupil dilatation in response to 100 Hz tetanus and an increase in remifentanil Ce(T) from 0 to 5 ng ml(-1) was found (R(2)=0.68). CONCLUSIONS: During propofol TCI in healthy patients, the decrease in pupil response to a painful stimulus is a better measurement of the progressive increase of remifentanil Ce(T) up to 5 ng ml(-1) than haemodynamic or BIS measurements.

Closed-loop control of propofol anaesthesia using bispectral index: performance assessment in patients receiving computer-controlled propofol and manually controlled remifentanil infusions for minor surgery.

BACKGROUND: In a previous study we used the bispectral index (BIS) for automatic control of propofol anaesthesia, using a proportional-integral-differential control algorithm. As control was less than optimal in some patients, we revised the constants of the control algorithm. The aim of the current study was to measure the performance of the revised system in patients undergoing minor surgery under propofol and remifentanil anaesthesia. METHODS: Twenty adult patients scheduled for body surface surgery were enrolled. Anaesthesia was manually induced with target-controlled infusions (TCI) of propofol and remifentanil. After the start of surgery, when anaesthesia was clinically adequate, automatic control of the propofol TCI was commenced using the revised closed-loop system. For patients 11-20, effect-site steering was also incorporated into the closed-loop control algorithm. Adequacy of anaesthesia during closed-loop control was assessed clinically, and by calculating the median performance error (MDPE), the median absolute performance error (MDAPE) and the mean offset of the control variable. RESULTS: The system provided adequate operating conditions and stable cardiovascular values in all patients during closed-loop control. The mean MDPE and MDAPE were -0.42% and 5.63%, respectively. Mean offset of the BIS from setpoint was -0.2. No patients reported awareness or recall of intraoperative events. CONCLUSIONS: The system was able to provide clinically adequate anaesthesia in all patients, with better accuracy of control than in the previous study. There was a tendency for more accurate control in those patients in whom the control algorithm incorporated effect-site steering.

Propofol sparing effect of remifentanil using closed-loop anaesthesia.

BACKGROUND: General anaesthesia is a balance between hypnosis and analgesia. We investigated whether an increase in remifentanil blood concentration would reduce the amount of propofol required to maintain a comparable level of anaesthesia in 60 patients undergoing ambulatory surgery. METHODS: Patients were allocated randomly to receive remifentanil to a target blood concentration of 2 ng ml(-1) (low), 4 ng ml(-1) (medium), or 8 ng ml(-1) (high), administered by target-controlled infusion (TCI). After equilibration, propofol TCI was commenced in closed-loop control, with auditory evoked potentials (AEPex) as the input signal, aiming for an AEPex of 35. This was to ensure a comparable and unbiased level of anaesthesia in all patients. RESULTS: We found a dose-dependent decrease in propofol requirements with increasing remifentanil concentrations. The mean (95% CI) propofol target blood concentration during adequate anaesthesia was 4.96 (3.85-6.01) micro g ml(-1) in the low, 3.46 (2.96-3.96) micro g ml(-1) in the medium, and 3.01 (2.20-3.38) micro g ml(-1) in the high group. There was no significant difference when recovery end points were achieved between the groups. Cardiovascular changes were moderate, but most pronounced in the high concentration group, with a decrease in heart rate of 21% compared with baseline. The mean calculated effect site propofol concentration at loss of consciousness was 2.08 (1.85-2.32) micro g ml(-1), and at recovery of consciousness was 1.85 (1.68-2.00) micro g ml(-1). CONCLUSIONS: This study confirms a synergistic interaction between remifentanil and propofol during surgery, whereas the contribution of remifentanil in the absence of stimulation seems limited. In addition, our results suggest that the propofol effect site concentration provides a guide to the value at which the patient recovers consciousness.

Relationship between bispectral index, auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points.

BACKGROUND: Many anaesthetists are deterred from using total i.v. anaesthesia because of uncertainty over the concentration of propofol required to prevent awareness. We predicted blood and effect-site concentrations of propofol at two clinical end-points: loss of consciousness and no response to a painful stimulus. METHODS: Forty unpremedicated Caucasian patients were anaesthetized with i.v. propofol delivered by a Diprifusor target-controlled infusion (TCI). Bispectral index (BIS) and auditory evoked potential index (AEPex) were measured and blood and effect-site propofol concentrations were predicted. Logistic regression was used to estimate population values for predicted blood and effect-site propofol concentrations at the clinical end-points and to correlate these with BIS and AEPex. RESULTS: The effect-site EC(50) at loss of consciousness was 2.8 micro m ml(-1) with an EC(05) and an EC(95) of 1.5 and 4.1 micro m ml(-1), respectively. The predicted EC(50) when there was no response to a tetanic stimulus was 5.2 micro m ml(-1) with an EC(05) and an EC(95) of 3.1 and 7.2 micro m ml(-1), respectively. CONCLUSIONS: Unconsciousness and lack of response to a painful stimulus occur within a defined range of effect-site concentrations, predicted by Diprifusor TCI software.

Patient-maintained sedation for oral surgery using a target-controlled infusion of propofol - a pilot study.

OBJECTIVE: To assess the safety and efficacy of a new patient-maintained propofol system for conscious sedation in dentistry. DESIGN: Prospective clinical trial SETTING: Department of Sedation, Glasgow Dental Hospital and School, 2001 SUBJECTS AND METHODS: Patients scheduled for oral surgery with conscious sedation. Exclusions included ASA IV -V, inability to use the handset, opioid use and severe respiratory disease. INTERVENTIONS: Patients were given intravenous propofol to a level of 1.0 microg/ml (reducing from 1.5 microg/ml) using a target controlled infusion system, they then controlled their sedation level by double-clicking a handset which on each activation increased the propofol concentration by 0.2 microg/ml. MAIN OUTCOME MEASURES: Oxygen saturation, patient satisfaction, and surgeon satisfaction. RESULTS: Twenty patients were recruited, 16 female and four male. Nineteen patients completed sedation and treatment successfully. Mean lowest oxygen saturation was 94%. No patients were over-sedated. All patients successfully used the system to maintain a level of sedation adequate for their comfort. Patient and surgeon satisfaction were consistently high. CONCLUSIONS: Initial experience with this novel system has confirmed safety, patient satisfaction and surgeon satisfaction.

Patient controlled administration of intravenous alfentanil during elective caesarean section under subarachnoid anaesthesia.

In this observational study, an alfentanil-containing patient controlled analgesia device was evaluated for the relief of visceral pain during elective caesarean section under subarachnoid anaesthesia. Forty healthy women at term received 2.5 mL of intrathecal hyperbaric 0.5% bupivacaine in the sitting position. Surgery began when loss of cold appreciation to the fourth thoracic dermatome was demonstrated. The patient controlled analgesia device was configured to deliver 3 microg.kg(-1) of alfentanil when first actuated. Each subsequent demand delivered 1.5 microg.kg(-1) with a 2-min lock-out interval. Sixty-five percent of women used alfentanil during surgery. The median (IQR) consumption of alfentanil was 360 (278-720) microg. Patient controlled analgesia is a useful method of supplementing subarachnoid anaesthesia for caesarean section. The technique is simple to use and in this group there were no troublesome side effects.

Closed loop control of sedation for colonoscopy using the Bispectral Index.

Sixteen patients undergoing colonoscopy were sedated with propofol using a closed-loop control system guided by the Bispectral Index (BIS). Propofol administration, via a target-controlled infusion, was controlled by a proportional-integral-differential control algorithm. The median (range) propofol target concentration during closed-loop control was 2.3 (1.7-3.6) microg.ml(-1). The performance characteristics of the system were excellent, with a median absolute performance error of 7 (1-15). Patients were drowsy yet rousable, with a median (range) BIS set-point of 80 (75-85). No patient became apnoeic, required airway support or became haemodynamically unstable whilst sedated. Eight patients moaned or moved during colonoscopy and four had recall. Median (range) time to full consciousness was 4 (2-20) min after the end of closed-loop control. Patient and surgeon satisfaction were high. We conclude that BIS may be a suitable control variable for closed-loop control of sedation with propofol.

Patient-maintained propofol sedation: a follow up safety study using a modified system in volunteers.

Patient-maintained sedation is a mode of patient-controlled sedation during which propofol is administered using a target-controlled infusion, with patient demand increasing the target concentration. A system tested previously for safety in our institution resulted in oversedation. Aiming to improve safety, we modified the system by increasing the lockout period to 4 min,reducing the starting concentration to 0.5 microg x ml(-1) and the increments on demand to 0.1 microg x ml(-1). As in the previous study, healthy volunteers attempted to render themselves unconscious by frequently pressing the demand button. To assess effects on memory, volunteers were given keywords to remember every 15 min. The maximum target concentration reached varied between 1.0 and 2.5 microg x ml(-1). No volunteers lost consciousness, however, one volunteer had a brief period of apnoea and oxygen desaturation. The Cp50 for loss of memory for words was 1.26 microg x ml(-1). Although this version represents an improvement, we conclude that the system is not yet completely suitable for use without anaesthetic supervision.

Propofol effective concentration 50 and its relationship to bispectral index.

Sixty unpremedicated healthy adult patients were studied during induction of anaesthesia with intravenous propofol delivered by a 'Diprifusor' target-controlled infusion. Bispectral index (BIS) and spectral edge frequency (SEF95) were measured concurrently with the predicted blood and effect site propofol concentrations. Logistic regression was used to calculate the predicted propofol blood and effect site concentrations required to produce unconsciousness and no response to a noxious stimulus in 50% and 95% of patients and to correlate BIS with these end-points. The Diprifusor TCI software produces anaesthesia at consistent target concentrations. Bispectral index correlates well with clinical end-points and may be useful during propofol anaesthesia.

Auditory evoked potential index predicts the depth of sedation and movement in response to skin incision during sevoflurane anesthesia.

BACKGROUND: The auditory evoked potential (AEP) index, which is a single numerical parameter derived from the AEP in real time and which describes the underlying morphology of the AEP, has been studied as a monitor of anesthetic depth. The current study was designed to evaluate the accuracy of AEPindex for predicting depth of sedation and anesthesia during sevoflurane anesthesia. METHODS: In the first phase of the study, a single end-tidal sevoflurane concentration ranging from 0.5 to 0.9% was assigned randomly and administered to each of 50 patients. The AEPindex and the Bispectral Index (BIS) were obtained simultaneously. Sedation was assessed using the responsiveness portion of the observer's assessment of alertness-sedation scale. In the second phase of the study, 10 additional patients were included, and the 60 patients who were scheduled to have skin incisions were observed for movement in response to skin incision at the end-tidal sevoflurane concentrations between 1.6 and 2.6%. The relation among AEPindex, BIS, sevoflurane concentration, sedation score, and movement or absence of movement after skin incision was determined. Prediction probability values for AEPindex, BIS, and sevoflurane concentration to predict depth of sedation and anesthesia were also calculated. RESULTS: The AEPindex, BIS, and sevoflurane concentration correlated closely with the sedation score. The prediction probability values for AEPindex, BIS, and sevoflurane concentration for sedation score were 0.820, 0.805, and 0.870, respectively, indicating a high predictive performance for depth of sedation. AEPindex and sevoflurane concentration successfully predicted movement after skin (prediction probability = 0.910 and 0.857, respectively), whereas BIS could not (prediction probability = 0.537). CONCLUSIONS: Auditory evoked potential index can be a guide to the depth of sedation and movement in response to skin incision during sevoflurane anesthesia.