Department of Anaesthesiology, Istanbul University, Istanbul Medical Faculty, Capa 34390, Istanbul, Turkey merthasta@yahoo.com
Accepted for publication: July 8, 2002
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Abstract |
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Methods. Sixty patients (three groups, n=20) undergoing lower abdominal surgery with total i.v. propofol anaesthesia were investigated. Patients in Group B received i.m. bupivacaine (5 mg ml1) 1 mg kg1, patients in Group L received i.m. lidocaine (100 mg ml1) 2 mg kg1 and patients in Group C received i.m. saline 5 ml before operation. Hypnosis was measured with bispectral index (BIS).
Results. The induction (BIS <45), and the maintenance doses of propofol (BIS between 40 and 50) were significantly less in Group B and Group L compared with the control group. Induction doses were 1.58 (SD 0.39), 1.56 (0.24) and 2.03 (0.33) mg kg1 respectively; P<0.0001. Maintenance doses were 6.33 (2.06), 7.08 (1.23) and 9.95 (2.02) mg kg1 respectively in the first hour; P<0.0001. Groups B and L were associated with an attenuated haemodynamic response to both induction and intubation.
Conclusion. I.M. administered local anaesthetics are associated with a decrease in both the induction and maintenance doses of propofol during total i.v. anaesthesia and a reduction in haemodynamic responses.
Br J Anaesth 2002; 89: 84952
Keywords: anaesthetic techniques, i.v.; anaesthetics local; monitoring, bispectral index
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Introduction |
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In previous studies it has been shown that i.m. administration of either lidocaine or bupivacaine enhances the hypnotic effects of i.v. thiopental5 and propofol.6 However, these studies only concluded that local anaesthetics administered i.m. can reduce the induction dose of i.v. general anaesthetics, no evaluation of the effect of systemically used local anaesthetics on the maintenance dose of the general anaesthetic was carried out. Additionally, the results of both studies were based on responses to verbal commands. More reliable results can be obtained using bispectral index (BIS), which has been shown to be a specific and sensitive monitor of the hypnotic component of anaesthesia.7 In a prospective, randomized, double-blind study, we investigated whether lidocaine or bupivacaine administered i.m. reduces the induction and the maintenance dose of propofol during BIS-guided total i.v. anaesthesia (TIVA).
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Methods |
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Patients did not receive premedication. They were prehydrated with NaCl 0.9% 500 ml solution, and were connected to an electrocardiograph monitor, automatic arterial pressure cuff and a pulse oximeter (Horizon 2000, Mennen Medical, Rehovot, Israel). BIS was monitored using a BIS sensor (Aspect Medical Systems, Natick, MA, USA) applied to the forehead as described by the manufacturer (BIS monitor Model A-2000TM, Aspect Medical Systems, Natick, MA, USA). Patients were then allocated randomly to one of three groups according to a sealed envelope technique in a double-blind manner. In Group B, 20 patients received i.m. bupivacaine (5 mg ml1) 1 mg kg1 (Marcaine 0.5% flk AstraZeneca I·laç A, Istanbul, Turkey), administered into the gluteus muscle 30 min before induction of anaesthesia. In Group L, 20 patients received i.m. lidocaine (100 mg ml1) 2 mg kg1 (Aritmal 10% ampul, Biosel I·laç A
, Istanbul, Turkey), administered into the gluteus muscle 10 min before induction of anaesthesia. In Group C, 20 patients served as controls and received i.m. saline 5 ml into the gluteus muscle 10 min before induction of anaesthesia. All i.m. injections were performed by an independent practitioner. HR, mean arterial pressure (MAP) and BIS values were recorded at t0 (before i.m. administration), t1 (before induction of anaesthesia), t2 (after induction of anaesthesia) and t3 (after intubation).
After a bolus dose of fentanyl 1.5 µg kg1 i.v., a physician, who was blinded to the dose or type of local anaesthetic (or saline) administered earlier, injected propofol 10 mg (1 ml) in 5 s every 15 s until the BIS score fell below 45. The total dose of propofol required to achieve a BIS below 45 was recorded in mg kg1. When BIS <45, response to verbal commands was evaluated. Tracheal intubation was accomplished after administration of rocuronium 0.6 mg kg1. Volume controlled ventilation (Dräger SA2, Drägerwerk, Lübeck, Germany) was started with 10 ml kg1 tidal volume and ventilatory frequency was adjusted to maintain endtidal carbon dioxide tension 3035 mm Hg. Lungs were ventilated with 50% oxygen, 50% air.
After intubation, infusion of propofol 10 mg kg1 h1 and remifentanil 0.25 µg kg1 min1 were started. The dose of propofol was titrated to keep the BIS score between 40 and 50. When the BIS score was out of these limits for 10 s the dose of propofol was changed by 1 mg kg1 h1 every 20 s. The total maintenance dose of propofol during the first hour of anaesthesia was recorded in mg kg1 h1.
Inadequate analgesia was defined as response to surgical stimuli by hypertension (SAP >20% above preoperative baseline value for >5 min) or tachycardia (HR >20% above preoperative baseline value), while BIS level was between 40 and 50. In cases of inadequate analgesia, patients were given bolus doses of remifentanil 0.5 µg kg1. If this treatment was unsuccessful, the remifentanil infusion rate was doubled.
Bradycardia was defined as HR <40 beat min1 and hypotension as a decrease in SAP >20% of the baseline value. Hypotension was treated by infusion of lactated Ringers solution 35 ml kg1, and if necessary, with ephedrine 5 mg i.v. Bradycardia was treated with atropine 0.5 mg i.v. The frequency of hypotension, bradycardia and inadequate analgesia and supplemental remifentanil doses was recorded.
To assess intraoperative awareness, a number was repetitively recited to each patient four times during anaesthesia at 5, 10, 15 and 20 min. The patients were specifically questioned for recall of this number.
Analysis of variance (ANOVA) was used to evaluate the differences in patient characteristics, HR, MAP, BIS-values, and propofol doses for induction and maintenance between the groups. Data at different times within the groups were compared with a repeated measures ANOVA (GraphPad InStatTM, GraphPad Software V2.02). The alterations in HR and MAP after the induction and intubation were also compared in the three groups. To compare the frequency of hypotension, bradycardia and inadequate analgesia, an appropriate 2-test was used. P<0.05 was regarded as statistically significant.
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Results |
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There were no differences between the BIS values before and after the injection (t0 and t1) of local anaesthetic/saline [95.1 (1.7) at t0 and 95.4 (0.8) at t1, P>0.05]. The difference between t2 and t3 was also not significant [43.2 (0.8) at t2 and 44.1 (2.0) at t3, P>0.05].
At the end of the induction period, no response to verbal commands was observed (BIS <45). Awareness or inadequate analgesia was observed in no patients. Except for the hypotension in two patients in each group, haemodynamic complications were not seen. No signs of local anaesthetic toxicity or side-effects were observed in any patient.
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Discussion |
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The interaction of local and general anaesthetics has been investigated in several studies. Hodgson and colleagues2 suggested three mechanisms for the reduction of MAC of volatile anaesthetic agents when combined with epidural anaesthesia: (i) systemic general anaesthetic effects of absorbed epidural lidocaine; (ii) direct epidural sensory block of the noxious stimulus and (iii) subanaesthetic concentrations of epidural lidocaine depressing spinal cord motor function. They concluded that the MAC-sparing effect of epidural anaesthesia in combination with general anaesthesia is most likely caused by central effects of spinal deafferentation, not to the systemic effects of lidocaine nor to direct neural block of spinal nerves. Our results do not support this conclusion. In another study it has been shown that i.v. lidocaine infusion has a MAC-sparing effect of 1028%.4 In our study, an i.v. anaesthetic has been used instead of inhalational anaesthetics, and lidocaine was administered via the i.m. route. It can be concluded that systemic general anaesthetic effects of absorbed local anaesthetics play an important role in the reduction of the dose of the general anaesthetic.
The effects of i.m. administration of lidocaine and bupivacaine on the induction doses of thiopental and propofol have been described.5 6 The results of these studies and the present study are similar. However, there are two important differences. Firstly, in our study, not only the induction, but also the maintenance doses of propofol were investigated. Secondly, in these studies the effects of local anaesthetics on the general anaesthetic effect of i.v. anaesthetics were shown and compared only by the responses to verbal commands and not by BIS. In our study, both the loss of response to commands and BIS were used.
According to several studies, there are two main mechanisms that may explain the interaction of local and general anaesthetics. Firstly, most local anaesthetics bind to sodium channels in the inactivated state, preventing subsequent channel activation and the large transient sodium influx associated with membrane depolarization.9 General anaesthetics are known to have some effects on the central nervous system, which are not unlike those of local anaesthetics. Both volatile anaesthetics and barbiturates have been shown to block sodium channels and thus prevent action potential formation in central neurones. Immobilization of the gating charge caused by the general anaesthetics has also been implicated in local anaesthetic action. Studies show that general anaesthetics do indeed increase the proportion of channels in the closed inactive state.1012
Secondly, it is well known that propofol enhances GABAergic currents, which facilitate inhibitory neurotransmission in neurones.13 Most i.v. anaesthetics inhibit the specific GABA uptake process in vitro in striatal nerve terminals, some, such as propofol, at clinically relevant concentrations.14 It has been shown that local anaesthetics also potentiate GABA-mediated Cl currents by inhibiting GABA uptake.15 These common mechanisms of action of local and general anaesthetics may explain how the hypnotic effect of i.v. propofol is enhanced by i.m. administration of bupivacaine or lidocaine.
We did not observe any signs of local anaesthetic toxicity or side-effects. The highest doses of local anaesthetics administered in our study were less than half the recommended maximum clinical doses16 and were similar to doses administered in previous studies.5 6 Further studies are necessary to evaluate the effects of different doses of both lidocaine and bupivacaine on the doses of general anaesthestics after i.m. administration. We administered i.m. lidocaine 10 min and i.m. bupivacaine 30 min before i.v. administration of propofol because, at these times, blood concentrations reach a peak.16
Changes in haemodynamic values were not the primary variable in our study. The attenuation of the cardiovascular response to intubation after i.v. lidocaine has been recognized for some time. However, there are few studies examining the effects of i.m. administration. Bupivacaine was associated with a more stable haemodynamic status after both induction and intubation compared with control and lidocaine. Similarly, both lidocaine and bupivacaine were associated with a reduced increase in heart rate after intubation. Whether these were caused by the reduction in propofol doses, or by the direct effect of the i.m.-administered local anaesthetics is unclear.
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Acknowledgements |
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References |
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