Department of Anaesthetics and Intensive Care Medicine, The Queens University of Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, UK*Corresponding author
LMA® is the property of Intavent Limited.
Accepted for publication: September 25, 2000
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Abstract |
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Br J Anaesth 2001; 86: 3615
Keywords: anaesthesia i.v., propofol; analgesics opioid, remifentanil; pharmacodynamics
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Introduction |
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It has been shown that the use of higher doses of remifentanil can result in the use of lower doses of propofol to prevent responses to tracheal intubation and surgery.5 However, it is not known if this has any influence on recovery. The aim of this study was to examine recovery with the use of remifentanil to supplement anaesthesia maintained with different preselected target plasma concentrations of propofol.
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Subjects and methods |
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Anaesthesia was induced and maintained with propofol using a target controlled infusion system (Diprifusor, Zeneca Ltd, Macclesfield, UK).6 7 The target plasma concentration for induction was set at 46 µg ml1. After loss of the eyelash reflex and verbal response, a bolus dose of remifentanil 1 µg kg1 was administered over 3060 s and infusion was started at an initial rate of 0.5 µg kg1 min1. Muscle relaxation, if required, was provided with rocuronium 0.5 mg kg1. The airway was maintained using a laryngeal mask airway (LMA) or a tracheal tube.
Patients were allocated randomly, using a computer-generated randomization scheme, to target plasma concentrations of propofol (CT) of 2, 3, 4 or 5 µg ml1 for maintenance of anaesthesia. The infusion rate of remifentanil was adjusted to provide adequate anaesthesia while maintaining the preselected CT constant. The patients lungs were ventilated with a mixture of 50% nitrous oxide in oxygen to maintain normocapnia. Anaesthesia was deemed to be adequate if heart rate and/or arterial pressure remained within 20% of baseline values and there was no movement, lachrymation or sweating in response to surgery. All patients received tenoxicam 20 mg and morphine 10 mg i.v. 1520 min before the expected end of surgery. The wound was infiltrated with bupivacaine. Neuromuscular block, when instituted, was monitored using a peripheral nerve stimulator and antagonized with neostigmine 50 µg kg1 in a mixture with glycopyrrolate 10 µg kg1.
Propofol, nitrous oxide and remifentanil were stopped when the last skin suture was applied and recovery from neuromuscular block had been ascertained.
The times to resumption of spontaneous respiration and extubation and/or LMA removal were recorded, as were times to opening the eyes on command, giving the correct date of birth, and orientation for date and time after cessation of all anaesthesia. The doses of remifentanil and propofol administered during the maintenance were recorded. Pain on arrival in the recovery ward was assessed using a 10 cm visual analogue scale (VAS; 0=no pain, 10=worst pain).
A Mini-Mental State (MMS) assessment questionnaire8 was administered before anaesthesia and 2 h after operation. An assessment was carried out at 4 h if the score had not returned to baseline at 2 h. The assessments of all recovery end-points and MMS assessments were carried out by an observer who was blinded to the group allocation of the patients.
The time when patients were ready for discharge from the recovery ward was recorded by the nursing staff (based on observation of control of pain, absence of emetic sequelae, and satisfactory cardiovascular and respiratory observations). The nursing staff were also unaware of the identity of the groups. The incidence of nausea or vomiting was recorded over the first 24 h period. The patients sense of well-being was scored the next day during the post-operative visit or by a telephone call (if already discharged) using a 10 cm VAS (0=feels lousy, 10=feels great). On the next day, patients were also asked three non-leading questions to look for evidence of recall. These were: What was the last thing you remember before going to sleep?; Did you have any dreams whilst you were under the anaesthetic?; and What was the first thing you remember when you woke up?
The continuous data were subjected to one-way analysis of variance, or the KruskalWallis tests, depending on the distributions or significant differences in variances, followed by post-tests if indicated [Bonferroni tests for ANOVA (analysis of variance) and Dunn tests for KruskalWallis tests]. The frequency distributions were subjected to 2 tests and differences were considered significant if P was <0.05. The statistical analysis was performed on a desktop computer using the Prism version 3.0 statistical software (Graph Pad, San Diego, CA, USA).
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Results |
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The doses of remifentanil and propofol used during the maintenance period (excluding the bolus doses given at induction) are given in Table 2. There was a significant difference between the groups in the dose of remifentanil administered [median 0.21, 0.15, 0.11 and 0.13 µg kg1 min1 in the 2, 3, 4 and 5 µg ml1 propofol groups respectively (P<0.01)]. The dose of propofol administered was also significantly different; as expected, it increased with increasing target concentration of propofol [0.08, 0.12, 0.16 and 0.20 mg kg 1 min1 (median values) in the four groups respectively (P<0.001)]. The doses of both remifentanil and propofol in the 13 patients receiving muscle relaxants were similar (remifentanil 0.120.30 µg kg1 min1 and propofol 0.080.09 mg kg1 min1 in the five patients in the 2 µg ml1 group; remifentanil 0.15 µg kg1 min1 and propofol 0.11 mg kg1 min1 in the one patient in the 3 µg ml1 group; remifentanil 0.080.16 µg kg1 min1 and propofol 0.15 mg kg1 min1 in the three patients in the 4 µg ml1 group; and remifentanil 0.050.25 µg kg1 min1 and propofol 0.190.23 mg kg1 min1 in the four patients in the 5 µg ml1 group).
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Discussion |
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It has been shown previously that opioids such as fentanyl and alfentanil exert a propofol-sparing effect, reducing its dose for maintenance of anaesthesia.9 10 We have demonstrated a propofol-sparing effect of remifentanil that allows a lower propofol CT to be used for maintenance of anaesthesia. However, the propofol-sparing effect of fentanyl was not associated with an improvement in recovery time.9 While propofol and alfentanil can be administered at different plasma concentrations to give an ideal ratio that could be used to give the most rapid return of consciousness, it requires a complicated step-down regime for both agents.10 Vuyk et al., using a computer simulation program, have also suggested that the propofol concentrations that allow the most rapid return of consciousness are lower when it is administered with remifentanil than when combined with alfentanil or fentanyl.11
Remifentanil is a unique drug, with rapid onset that allows rapid intraoperative titration dependent upon clinical needs, and rapid and predictable offset. It also has a short and constant context-sensitive half-life.2 12 Regardless of the duration of infusion, the decrease in plasma concentration to 50% has a time of 3.6 min.12 These characteristics allow uncomplicated changes in infusion rates with rapid effect, making remifentanil an ideal adjunctive agent for i.v. anaesthesia. The present study has clearly shown the influence of its use on early recovery.
As expected, patients in the groups receiving the higher CTs of propofol received significantly more propofol and those receiving the lower concentrations received significantly more remifentanil. By changing the balance of the anaesthetic agents and maintaining the same qualitative anaesthetic, patients in the 2 and 3 µg ml1 CT groups had more rapid recovery and return of orientation. This was obviously because of the unique characteristics of remifentanil. However, in spite of early post-operative recovery in patients given the higher supplementation doses of remifentanil, there were no significant differences in the times when patients were ready for discharge from the recovery ward (although there was a trend towards a shorter time in the 2 µg ml1 group) or in the patients perception of well-being. This has been shown in another study recently, in which the use of remifentanil was associated with faster, early recovery but with no difference in discharge from the recovery ward and patient satisfaction.13 This indicates a useful effect of remifentanil supplementation only in the early post-operative period. This is perhaps what would be expected from a drug with a short duration of action. The actual discharge from the recovery ward may be influenced by other factors, such as post-operative pain or nausea and vomiting. The nurses preconception of a minimal period of stay in the recovery ward may also play a role. It is our impression that, despite the availability of more rapidly-acting anaesthetic agents and faster recovery times, the actual time of discharge of patients from the recovery ward may be delayed by paperwork and logistic difficulties such as portering and the availability of surgical ward nursing staff to accept patients, factors over which anaesthetists may have little control. This has also been noted by others14 15 and needs to be examined if full use is to be made of the advantages of new drugs and techniques. Nevertheless, an advantage in terms of early recovery is also useful, and would result in less need for intensive nursing supervision.
The MMS assessment has been used previously by Chung in assessing the return of higher mental function in the elderly after neuroleptanaesthesia.8 We, however, found little difference in these scores between the groups pre-operatively, and little difference between pre- and postoperative scores within each group. The MMS score may be an insensitive measure of recovery after administration of short-acting agents, or it may be more useful when applied at an earlier time. No patient had recall of any intra-operative events, although most could recall waking up in the operating theatre after surgery.
A possible disadvantage of the use of remifentanil as the intra-operative opioid is the absence of immediate postoperative analgesia. This was taken into consideration in the present study by administration of morphine and tenoxicam, and infiltration of the wound with bupivacaine before termination of anaesthesia. This resulted in most patients being comfortable in all groups (no significant difference in VAS scores) but did not affect post-anaesthetic recovery, and may be of advantage in moderately painful procedures performed on day-case surgical patients.
In conclusion, the results of our study show shorter recovery times when maintenance of anaesthesia is changed from using a higher dose of propofol with a lower dose of remifentanil to a regime with a lower dose propofol and a higher dose of remifentanil. However, the advantages are limited to early recovery.
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Acknowledgement |
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References |
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2 Kaplia A, Glass PSA, Jacobs JR et al. Measured context-sensitive half-times for remifentanil and alfentanil. Anesthesiology 1995; 83: 96875[ISI][Medline]
3 Glass PSA, Hardmann D, Kamiyama Y et al. Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil (G187084B). Anesth Analg 1993; 77: 103140[Abstract]
4 Selinger K, Natin RL, Smith GA. Enzymatic and chemical hydrolysis of remifentanil. Anesthesiology 1995; 83: A834[ISI]
5 Fragen RJ, Randel GI, Librojo ES et al. The interaction of remifentanil and propofol to prevent response to tracheal intubation and the start of surgery for outpatient knee arthroscopy. Anesthesiology 1994; 81: A376
6 White M, Kenny GNC. Intravenous propofol anaesthesia using a computerised infusion system. Anaesthesia 1990; 45: 2049[ISI][Medline]
7 Swinhoe CF, Peacock JE, Glen JB, Reilly CS. Evaluation of the predictive performance of a Diprifusor TCI system. Anaesthesia 1998; 53 (Suppl 1): 617[ISI][Medline]
8 Chung F, Lavelle PA, McDonald S, Chung A, McDonald NG. Cognitive impairment after neuroleptanalgesia in cataract surgery. Anesth Analg 1988; 64: 6148
9 Thomas VL, Sutton DN, Saunders DA. The effect of fentanyl on propofol requirements for day case anaesthesia. Anaesthesia 1988; 43 (Suppl): 735[Abstract]
10 Vuyk J, Lim T, Engbers FH et al. The pharmacodynamic interaction of propofol and alfentanil during lower abdominal surgery in women. Anesthesiology 1995; 83: 822[ISI][Medline]
11 Vuyk J, Mertens MJ, Olofsen E, Burm AGL, Bovill JG. Propofol anesthesia and rational opioid selection. Determination of optimal EC50-EC95 propofol-opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology 1997; 87: 154962[ISI][Medline]
12 Westmoreland CL, Hoke JF, Sebel PS. Pharmacokinetics of remifentanil (GI87084) and its major metabolite (GI90291) in patients undergoing elective inpatient surgery. Anesthesiology 1993; 79: 893903[ISI][Medline]
13 Loop T, Priebe H-J. Recovery after anesthesia with remifentanil combined with propofol, desflurane or sevoflurane for otorhinolaryngeal surgery. Anesth Analg 2000; 91: 1239
14 Seago JA, Weitz S, Walczak S. Factors influencing stay in the postanesthesia care unit: a prospective analysis. J Clin Anesth 1998; 10: 57987[ISI][Medline]
15 Pavlin DD, Rapp SE, Polissar NL, Malmgren JA, Koerschgen M, Keyes H. Factors affecting discharge in adult outpatients. Anesth Analg 1998; 87: 81626[Abstract]