Early recovery after remifentanil-pronounced compared with propofol-pronounced total intravenous anaesthesia for short painful procedures{dagger}

C. Hackner, O. Detsch*, G. Schneider, S. Jelen-Esselborn and E. Kochs

Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaningerstr. 22, D-81675 Munich, Germany

Corresponding author. E-mail: o.detsch@lrz.tum.de
{dagger}Presented in part at the annual meeting of the American Society of Anesthesiologists, Orlando, USA, October 2002.

Accepted for publication: June 2, 2003


    Abstract
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Background. We compared recovery from high-dose propofol/low-dose remifentanil (‘propofol-pronounced’) compared with high-dose remifentanil/low-dose propofol (‘remifentanil-pronounced’) anaesthesia.

Methods. Adult patients having panendoscopy, microlaryngoscopy, or tonsillectomy were randomly assigned to receive either propofol-pronounced (propofol 100 µg kg–1 min–1; remifentanil 0.15 µg kg–1 min–1) or remifentanil-pronounced (propofol 50 µg kg–1 min–1; remifentanil 0.45 µg kg–1 min–1) anaesthesia. In both groups, the procedure was started with remifentanil 0.4 µg kg–1, propofol 2 mg kg–1, and mivacurium 0.2 mg kg–1. Cardiovascular measurements and EEG bispectral index (BIS) were recorded. To maintain comparable anaesthetic depth, additional propofol (0.5 mg kg–1) was given if BIS values were greater than 55 and remifentanil (0.4 µg kg–1) if heart rate or arterial pressure was greater than 110% of pre-anaesthetic values.

Results. Patient and surgical characteristics, cardiovascular measurements, and BIS values were similar in both groups. There were no differences in recovery times between the groups (time to extubation: 12.7 (4.5) vs 12.0 (3.6) min, readiness for transfer to the recovery ward: 14.4 (4.4) vs. 13.7 (3.6) min, mean (SD)).

Conclusions. In patients having short painful surgery, less propofol does not give faster recovery as long as the same anaesthetic level (as indicated by BIS and clinical signs) is maintained by more remifentanil. However, recovery times were less variable following remifentanil-pronounced anaesthesia suggesting a more predictable recovery.

Br J Anaesth 2003; 91: 580–2

Keywords: anaesthetic techniques, i.v.; anaesthetics i.v., propofol; analgesics opioid, remifentanil; brain, electroencephalography; recovery


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Rapid and predictable recovery from anaesthesia are both important goals of anaesthesia. Remifentanil may help to reach these goals.15 Since remifentanil—as a potent opioid—does not induce adequate hypnosis,6 it is usually combined with a hypnotic, such as propofol. When propofol is combined with alfentanil, treatment of signs of light anaesthesia with alfentanil gives faster recovery than treatment with additional propofol.2 For remifentanil, which has an even shorter half-life than alfentanil, no data are available. We therefore compared early recovery from anaesthesia using high-dose propofol/low-dose remifentanil (‘propofol-pronounced anaesthesia’) and high-dose remifentanil/low-dose propofol (‘remifentanil-pronounced anaesthesia’) for short, painful surgery.


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
After approval from the local ethics committee and written informed consent, we prospectively studied 44 adult patients (aged 18–73 yr; ASA I–III) of both genders undergoing elective panendoscopy, microlarygoscopy, or tonsillectomy. We excluded patients with a history of neurological or psychiatric disorder, chronic use of centrally acting medication, and a BMI greater than 35. Patients received no pre-medication. Before induction, patients were randomized to receive either a propofol-pronounced (propofol 100 µg kg–1 min–1, remifentanil 0.15 µg kg–1 min–1) or a remifentanil-pronounced (propofol 50 µg kg–1 min–1, remifentanil 0.45 µg kg–1 min–1) anaesthesia. The anaesthetist providing anaesthesia and the interviewer recording all variables were blinded to the drug concentrations. In both groups anaesthesia was induced with remifentanil (0.4 µg kg–1 over 30 s), followed by propofol (2.0 mg kg–1 over 30 s) and mivacurium (0.2 mg kg–1). The trachea was intubated and the lungs mechanically ventilated (FIO2 0.3–0.4) to maintain normocapnia. Continuous drug infusions were started immediately after the induction doses and were stopped at the end of surgery; that is when the surgeon removed the laryngoscope or mouth gag. Neuromuscular block (monitored with a nerve stimulator) was maintained with mivacurium according to surgical requirements. Non-invasive mean arterial pressure (MAP), electrocardiographic heart rate (HR), end-tidal carbon dioxide pressure, pulse oximetry (SpO2), and the EEG-derived bispectral index (BIS) were measured continuously. BIS was measured with an Aspect A1000 monitor (BIS v. 3.3, Aspect Medical Systems Inc., Natick, USA). To provide adequate depth of anaesthesia for both groups, remifentanil (0.4 µg kg–1) was given if HR or MAP was greater than 110% of pre-induction baseline, or propofol (0.5 mg kg–1) was given when BIS was greater than 55. Before leaving the recovery room and on the day after anaesthesia, patients were asked about awareness and recall.

Values of MAP, HR, SpO2, and BIS were recorded at 1-min intervals during induction and emergence, and at 5-min intervals during maintenance. The times from stopping the infusions to eye opening (verbal command repeated every 15 s), to spontaneous respiration, to extubation, and to readiness for transfer to the recovery ward (based on adequate respiration, stable arterial pressure, HR, and response to command) were recorded. Data are given as mean (SD) or number of patients. For statistical analysis, t-tests for paired and unpaired data, and {chi}2-tests were used, as appropriate. A Bonferroni-adjusted P<0.05 was considered significant. A sample size calculation before the study ({alpha}=0.05, ß=0.8) based on the results of a pilot study suggesting a sample size of 21 patients in each group should detect a 3-min reduction in readiness for discharge to the recovery unit.

Forty-four patients were enrolled. One patient was excluded because of changes in the surgical procedure. The groups did not differ with respect to patient characteristics, type and duration of surgery, and duration of infusion of propofol/remifentanil (Table 1). The number of patients given additional doses of propofol and remifentanil and the number of doses did not differ between groups. There were no significant differences between groups for MAP, HR, and BIS values at any time in the study. Mean recovery times (resumption of spontaneous ventilation, eye opening, extubation, or readiness for transfer to the recovery ward) did not show significant differences between groups. However, the ranges of all recovery variables were less in the remifentanil-pronounced group; for example, the range for the time to extubation and readiness for transfer to the recovery ward were 21 and 20 min in the propofol-pronounced group compared with 11 and 12 min in the remifentanil-pronounced group. There were no differences between groups in drug usage (analgesics, antiemetics) and nausea/vomiting in the recovery ward. No intra-operative awareness with recall was reported.


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Table 1 Patient and surgical characteristics, duration of infusion of propofol/remifentanil, additional propofol and remifentanil bolus doses, BIS, heart rate, arterial pressure, and recovery times. Values are mean (SD), range, or number of patients (n). There were no significant differences in any variable between both groups. *P<0.05 vs pre-anaesthetic baseline; #minutes after discontinuation of drugs
 

    Comment
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
We did not find significant differences in mean early recovery times between the propofol-pronounced and the remifentanil-pronounced anaesthesia. A reduced propofol dose does appear to shorten recovery as long as the same anaesthetic depth (as indicated by BIS and clinical signs) is maintained with a greater remifentanil dose. When comparing the effects of different doses of anaesthetics on recovery, a comparable depth of anaesthesia is very important, particularly at the start of recovery.2 5 Preliminary data suggested that more remifentanil allows for a decrease in propofol dose without altering anaesthetic depth, judged by the absence of responses to noxious stimuli.7 A recent study4 suggested that less propofol and more remifentanil could speed early recovery. However, in that study depth of anaesthesia was assessed only by clinical signs, which are affected by opioid administration and thus, may be of limited value as a monitor of hypnotic effects. We used haemodynamic parameters in conjunction with EEG-based monitoring (BIS) to assess and to adjust anaesthetic depth. The BIS is a processed EEG parameter that indicates the effects of anaesthetics on the brain;8 for example, it was demonstrated that the BIS reflects changes of anaesthetic depth induced by remifentanil during propofol anaesthesia.9 In our study, heart rate, arterial pressure, and BIS values did not show differences throughout the study, suggesting that both groups were maintained at the same level of anaesthesia.

In the study, additional anaesthetic doses were given when anaesthesia was deemed inadequate. This may be a weakness of the study design, because it could increase the infusion rate of the ‘low dose’ drug, which may end up being a ‘high dose’ rate; however, this did not take place in our patients. For remifentanil, additional doses were small and similar between groups and infusion rates remained nearly unchanged. For propofol, dose adjustment increased the total propofol dose by approximately 50 µg kg–1 min–1 in both groups; that is propofol doses in both groups were increased as compared with the intended drug regimen, but the difference between ‘high’ and ‘low’ propofol dose was maintained.

A fast and predictable emergence from anaesthesia can improve efficiency of operating theatre use, especially in surgery with a rapid turn-over. In the present study, panendoscopies, microlaryngoscopies, and tonsillectomies were chosen. These include laryngoscopy during surgery, which is an intensely painful stimulus.10 Deep analgesia and hypnosis are required until the end of surgery, which can prolong emergence. We found no decrease in mean recovery times. However, for efficient operating theatre scheduling, not only the average recovery times but also the variation of these times are important. Our data show a smaller variability (i.e. smaller range) of recovery times following remifentanil-pronounced anaesthesia. This suggests predictable emergence and may help in scheduling operating theatre allocations. A shortcoming of our study is that we did not measure intermediate recovery such as discharge from the recovery ward. However, an effect on intermediate recovery was not expected, as previous studies have shown that the use of remifentanil only affects early recovery.3 4 In addition, the actual discharge from the recovery ward may be highly influenced by logistic factors or a preconception of a minimal period of stay in the recovery ward.4


    Acknowledgement
 
The authors are grateful to Prof. K. Ulm (Institut für Medizinische Statistik und Epidemiologie, Technische Universität München, Germany) for advice in statistics. This study was exclusively funded from departmental sources.


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
1 Rowbotham DJ, Peacock JE, Jones RM, et al. Comparison of remifentanil in combination with isoflurane or propofol for short-stay surgical procedures. Br J Anaesth 1998; 80: 752–5[Abstract/Free Full Text]

2 Monk TG, Yifeng D, White PF. Total intravenous anesthesia: effects of opioid versus hypnotic supplementation on autonomic responses and recovery. Anesth Analg 1992; 75: 798–804[Abstract]

3 Loop T, Priebe HJ. Recovery after anesthesia with remifentanil combined with propofol, desflurane, or sevoflurane for otorhinolaryngeal surgery. Anesth Analg 2000; 91: 123–9[Abstract/Free Full Text]

4 O’Hare RA, Mirakhur RK, Reid JE, Breslin DS, Hayes A. Recovery from propofol anaesthesia supplemented with remifentanil. Br J Anaesth 2001; 86: 361–5[Abstract/Free Full Text]

5 Wuesten R, Van Aken H, Glass PSA, Buerkle H. Assessment of depth of anesthesia and postoperative respiratory recovery after remifentanil- versus alfentanil-based total intravenous anesthesia in patients undergoing ear-nose-throat surgery. Anesthesiology 2001; 94: 211–7[ISI][Medline]

6 Lang E, Kapila A, Shlugman D, Hoke JF, Sebel PS, Glass PSA. Reduction of isoflurane minimal alveolar concentration by remifentanil. Anesthesiology 1996; 85: 721–8[ISI][Medline]

7 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

8 Johansen JW, Sebel PS. Development and clinical application of electroencephalographic bispectrum monitoring. Anesthesiology 2000; 93: 1336–44[ISI][Medline]

9 Koitabashi T, Johansen JW, Sebel PS. Remifentanil dose/electroencephalogram bispectral response during combined propofol/regional anesthesia. Anesth Analg 2002; 94: 1530–3[Abstract/Free Full Text]

10 Zbinden AM, Petersen-Felix S, Thomson DA. Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia. II. Hemodynamic responses. Anesthesiology 1994; 80: 261–7[ISI][Medline]





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