Department of Neuroscience, Psychiatric and Anesthesiological Sciences, University of Messina, School of Medicine, Policlinico Universitario G. Martino, Messina, Italy
* Corresponding author: Department of Neuroscience, Psychiatric and Anesthesiological Sciences, Policlinico Universitario, via C. Valeria, 98125 Messina, Italy. E-mail: vfodale{at}unime.it
Accepted for publication May 6, 2005.
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Abstract |
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Methods. Forty-six adult patients, ASA IIII, scheduled for elective minor surgical procedures were studied. Patients were premedicated with remifentanil infusion 0.4 µg kg1 min1 and anaesthesia was induced 45 min later with propofol 1.5 mg kg1 and maintained with airoxygen ( 0.4), remifentanil 0.10.15 µg kg1 min1 and sevoflurane, adjusted to keep the BIS between 40 and 50. After 20 min of stable anaesthesia, the subjects were allocated randomly to receive i.v. tramadol 1.5 mg kg1 and i.v. ketorolac 0.3 mg kg1 (tramadol group) or saline (control group). BIS values, mean arterial pressure, heart rate and end-tidal carbon dioxide were recorded every 5 min for 20 min.
Results. Mean BIS values after tramadol administration were not significantly different from those recorded in patients receiving saline throughout the period of observation. There were no patients who presented explicit recall of events under anaesthesia. No significant changes in mean arterial pressure, heart rate and end-tidal carbon dioxide were noted after tramadol injection.
Conclusion. Tramadol, given with ketorolac to prevent postoperative pain, during anaesthesia maintained with sevoflurane and remifentanil at BIS between 40 and 50, does not modify the BIS value.
Keywords: anaesthesia, depth ; analgesics opioid, tramadol
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Introduction |
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The Bispectral Index (BIS) is a processed electroencephalographic monitor introduced to evaluate the depth of anaesthesia and prevent the risk of awareness.6 Nevertheless, there is a lack of data about the effects of tramadol on BIS during anaesthesia. Because tramadol appears to affect EEG activity, the aim of this study was to investigate the effects of tramadol, administered along with ketorolac, on BIS in patients anaesthetized with sevoflurane and remifentanil.
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Methods |
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On arrival in the anaesthetic room, standard monitoring was started with continuous ECG, non-invasive arterial blood pressure measurement, pulse oximetry, BIS (BIS® XP, software version 3.12, four-electrode sensor; Aspect Medical Systems, Newton, MA, USA) and capnography. The BIS electrode (four-electrode sensor) was positioned on each patient's forehead as recommended by the manufacturer.
In all patients, induction of anaesthesia was started with a remifentanil infusion at 0.4 µg kg1 min1 and 45 min later propofol 1.5 mg kg1. Neuromuscular blockade was obtained with cisatracurium 0.1 mg kg1. A tracheal tube was inserted and the lungs were ventilated with air and oxygen ( 0.4). Immediately after intubation, remifentanil was reduced to 0.10.15 µg kg1 min1. Controlled ventilation was adjusted to maintain normocapnia. Anaesthesia was maintained with sevoflurane. The concentration of sevoflurane and the infusion rate of remifentanil were adjusted to maintain the value of BIS between 40 and 50.7 8
Thirty minutes before the end of anaesthesia, the patients were allocated randomly to receive i.v. tramadol 1.5 mg kg1 and ketorolac 0.3 mg kg1 (tramadol group), or saline (control group). In a preliminary study (data not shown), administration of ketorolac did not change the BIS values. All haemodynamic and BIS variables were recorded at the following time intervals: before administration of tramadol or saline (0 min) and 5, 10, 15 and 20 min after administration of tramadol (along with ketorolac), as previously described by Coetzee and colleagues.9 After administration of the study medications and during the period of observation, the concentration of sevoflurane and the infusion rate of remifentanil were not modified. During data collection, the investigator was blinded to the group allocation of the patient.
In the postanaesthesia care unit just before transfer to the ward, the patients were interviewed using modified Brice interview;10 this aims to evaluate the possible occurrence of awareness.
Statistics
Data were expressed as mean (SD). Demographic values were analysed with the 2 test and one-way analysis of variance. The values of BIS, heart rate, mean arterial pressure and end-tidal carbon dioxide (
) were analysed using Student's t-test for independent groups; P<0.05 was considered statistically significant.
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Results |
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Discussion |
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There is a lack of data regarding the effects of tramadol on BIS, a processed electroencephalographic monitor introduced to monitor the depth of anaesthesia.6 There is also a lack of data about the effects of tramadol on sedation and hypnosis. Nevertheless, previous clinical studies have speculated on the intraoperative effects of tramadol on EEG activity. Coetzee and colleagues9 reported that, during anaesthesia with isoflurane and nitrous oxide, tramadol caused significant dose-dependent activation of the EEG, as seen by increased frequencies and decreased amplitudes, but these changes were small and probably unimportant. Derived EEG variables did not approach values known to be associated with near-awakening during isoflurane anaesthesia; no patient moved on skin incision and there were no incidences of free recall.9 Later, Coetzee and colleagues5 confirmed that, although tramadol may cause awareness and EEG activation during anaesthesia, it does not antagonize the hypnotic effects of volatile anaesthetics. Vaughan and colleagues4 suggested dose-related activation with tramadol in all EEG variables during anaesthesia with isoflurane and nitrous oxide. EEG changes were not at levels thought to be associated with awareness, indicating that tramadol, whilst causing EEG activation, has no effect on depth of anaesthesia.4
Unlike previous clinical studies, our data did not show any evidence of BIS modification when tramadol was given in clinical doses to prevent postoperative pain. Therefore, the significance of previous findings of EEG activation by tramadol is difficult to interpret. Nevertheless, several hypotheses are possible. In the studies by Vaughan and colleagues4 and Coetzee and colleagues,9 low concentrations of volatile anaesthetic with nitrous oxide were administered. It is likely that the EEG-activating effect of tramadol may also depend on the concentration of the volatile anaesthetics. This is supported by the fact that the British National Formulary did not recommend the use of tramadol during light anaesthesia.11
Also, the presence of nitrous oxide could have played a role in the excitatory property of tramadol. In animals, an increase in EEG activity has been shown when nitrous oxide is added to low concentrations of isoflurane,12 with a potentially facilitating activation effect of tramadol. In particular, the difference between modification of EEG patterns and evoked potential shown by Vaughan and colleagues4 after tramadol administration contradicts a possible role of nitrous oxide, since a different effect on EEG and cortical somatosensory evoked potentials (SEP) was seen when nitrous oxide was added to isoflurane anaesthesia.13 In addition, different anaesthetic drugs can produce different electroencephalographic patterns. Increases in delta activity are interpreted as signs of modification of depth of anaesthesia. These EEG patterns are sometimes also found in frontal leads after surgical stimulation during isoflurane anaesthesia, which leads to the conclusion that, to avoid incorrect anaesthetic management under EEG monitoring, this phenomenon of paradoxical arousal must be taken into consideration.14
Finally, the dosage of tramadol could also have played a role, since we administered clinical doses of the drug. This hypothesis is consistent with previous studies in which excitatory effects in the central nervous system were observed only when tramadol was given at doses exceeding the therapeutic range.15
This study has some limitations. First, the small number of patients may have hidden some true variation. But the number of patients included in each group was higher than in previous studies evaluating the EEG effects of tramadol during anaesthesia.4 9 Secondly, there are limitations in the study protocol. It reflects our daily clinical practice, in which we maintain BIS values between 40 and 50. Tramadol did not change the BIS value in this deep hypnotic state. Nevertheless, the effect of tramadol on patients under relatively light anaesthesia might cause an arousal reaction, and furthermore it might increase the presence of explicit memory. The light general anaesthesia (with sufficient analgesia) could otherwise reflect the daily clinical practice of other anaesthetists. In addition, we administered tramadol during surgery, whereas Vaughan and colleagues4 tested the drug before surgery. Surgery stimulation plays an important role in the modification of the depth of anaesthesia, or occurrence and recall of intraoperative awareness. However, our study reflects the common clinical practice of giving analgesics intraoperatively to prevent postoperative pain. Thirdly, tramadol was administrated along with ketorolac. But ketorolac does not act on the central nervous system, and therefore in our study the results could not have been modified by the co-administration of ketorolac. Moreover, co-administration of ketorolac reproduces a method of treatment of postoperative pain commonly applied during anaesthesia.16
The use of the BIS in monitoring EEG modification could also be criticized, compared with previous studies.4 9 Nevertheless, electroencephalographic parameters evaluated during nitrous oxide and isoflurane anaesthesia are well correlated with BIS at surgical levels,17 and BIS is known to give more information than power spectrum-based analysis.18
In conclusion, administration of tramadol, together with ketorolac, to prevent postoperative pain does not further modify the values of BIS during anaesthesia with sevoflurane and remifentanil when the BIS is kept between 40 and 50.
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References |
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