Anesth Analg 2003;97:461-464
© 2003 International Anesthesia Research Society
ANESTHETIC PHARMACOLOGY
The Effect of Mixing Lidocaine with Propofol on the Dose of Propofol Required for Induction of Anesthesia
Li-Hoon Tan, Mmed (Anaesthesiology)*, and
Nian-Chih Hwang, FFARCSI FAMS
Department of Anaesthesia and Surgical Intensive Care, *Changi General Hospital, and
Singapore General Hospital, Singapore, Singapore
Address correspondence and reprint requests to Dr. Li-Hoon Tan, Department of Anaesthesia and Surgical Intensive Care, Changi General Hospital, 2 Simei St. 3, Singapore 529889, Singapore. Address e-mail to Li_Hoon_Tan{at}cgh.com.sg
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Abstract
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Lidocaine is used to reduce pain associated with propofol injection, either mixed with propofol or preceding it as a separate injection. The addition of lidocaine to propofol causes destabilization of the emulsion and reduces anesthetic potency in rats and humans. We conducted a randomized double-blinded study on 67 patients to assess the effect of mixing lidocaine with propofol on the dose of propofol required for the induction of anesthesia. Patients in Group S (n = 32) received IV lidocaine 0.2 mg/kg followed by an infusion of propofol whereas those in Group M (n = 35) received IV normal saline (placebo) followed by an infusion of a freshly prepared mixture of propofol 1%/lidocaine 1% in 10:1 volume ratio. The infusion was stopped when the subjects lost consciousness, as detected by the syringe-drop method. There was no statistically significant difference between the two groups in the mean (95% confidence interval) doses of propofol required for loss of consciousness: 2.0 (1.8–2.2) mg/kg for Group S versus 1.9 (1.7–2.0) mg/kg for Group M (P = 0.206). Mixing 20 mg of lidocaine with 200 mg of propofol is unlikely to affect the dose of propofol required for the induction of anesthesia.
IMPLICATIONS: Adding lidocaine to propofol destabilizes the propofol emulsion. A randomized double-blinded trial found no statistically significant difference in the doses of propofol required for the induction of anesthesia whether administered as a freshly prepared propofol 1%/lidocaine 1% 10:1 mixture or as a separate injection after a dose of lidocaine.
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Introduction
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Lidocaine is widely used to reduce the pain associated with injection of propofol (1–10), administered either mixed with propofol or as a separate injection. When given before injection of propofol, it is sometimes administered as a mini-Bier’s block, using a tourniquet that is released after 30–120 s (1–4).
Propofol is formulated as a 1% emulsion. The addition of lidocaine to the emulsion destabilizes the emulsion in a dose- and time-dependent manner (11). The administration of propofol as a propofol/lidocaine mixture also reduces its anesthetic potency in rats and women (8,12).
We compared two common clinical practices to determine whether there is a difference in the dose of propofol required for the induction of anesthesia, as measured by the syringe-drop method, between administering propofol as a freshly prepared propofol/lidocaine mixture and as a separate injection after pretreatment with lidocaine using a forearm tourniquet.
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Methods
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This study was conducted after approval by the hospital medical ethics committee. Written informed consent was obtained from all patients, or the parents for patients under 21 yr of age. Seventy patients, aged 18–50 yr, of ASA physical status I and II, presenting for elective surgery under general anesthesia, were recruited. Exclusion criteria included obesity (body mass index >30 kg/m2), pregnancy, risk of aspiration of gastric contents, suspected or known difficult airway, presence of central nervous system disease, use of medications likely to affect the central nervous system, significant cardiac or liver dysfunction, and hypersensitivity to study drugs. No premedication was given.
The solutions used were propofol 1% (Abbott Laboratories, North Chicago, IL) and lidocaine 1% (Pharmacia & Upjohn, Bentley, Australia). One investigator (LHT) prepared the drugs and programmed the infusion pump in the absence of a blinded observer. This observer was blinded to the drugs used and the infusion rate display on the pump, which was hidden from view by an opaque cover.
An 18-gauge venous cannula was inserted into a forearm vein and flushed with 10 mL of normal saline over 5 s to ensure pain-free injection. Routine monitors were used and the data recorded every minute.
Each patient was preoxygenated via facemask with a fresh gas flow of 6 L/min oxygen for 3 min. A forearm tourniquet of adequate tightness to cause engorgement of the veins on the dorsum of the hand was applied. The patients were randomly assigned to one of two groups using a computer-generated list. Group S (Separate) patients received 0.2 mg/kg lidocaine 1% (0.02 mL/kg) with the tourniquet released after 1 min, followed by an infusion of propofol 1% at 300 mL/h (50 mg/min). Group M (Mixed) patients received 0.02 mL/kg normal saline with the tourniquet released after 1 min, followed by an infusion of a freshly prepared mixture of propofol 1%/lidocaine 1% in a 10:1 volume ratio, at a rate of 330 mL/h (equivalent to 50 mg of propofol/min). The rate of 50 mg/min of propofol was chosen to maintain uniformity among the patients. The first injection (lidocaine or saline) was administered via a port on the venous cannula. The infusions were administered with a syringe pump, IV accurate control total IV anesthesia (ALARIS Medical Systems, Hampshire, UK), via a three-way tap just proximal to the venous cannula. A fast-running infusion of Ringer’s lactate solution was started together with the propofol or propofol/lidocaine infusion.
Forty seconds after the start of the infusion, the patients were asked by the blinded observer to report any sensation in the upper limb and grade the severity of pain, if any, using a three-point scale (mild, moderate, severe).
The end point of induction, taken as the dropping of a water-filled 20-mL syringe held between the thumb and index finger of an extended arm (13), was also assessed by the observer. The propofol or propofol/lidocaine infusion was stopped when the syringe was dropped and general anesthesia was continued as per routine practice. The induction time was considered as the time from the start of the propofol infusion to the dropping of the weighted syringe and the induction dose of propofol as the amount of propofol infused over this time.
Statistical analysis was conducted using SPSS for Windows release 10.0 (SPSS, Chicago, IL). The study size was adequate to detect a difference in the induction dose of propofol of 0.5 mg/kg with 
= 0.05 and power of 0.9, based on previously published data (14). Numerical data were compared with Student’s t-test, categorical demographic data with 
2 test, and pain scores with Mann-Whitney U-test. Statistical significance was taken as P < 0.05.
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Results
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Three patients from Group S were excluded from analysis because of protocol violation, leaving 32 patients in Group S and 35 patients in Group M.
There were no statistically significant differences between the groups with respect to demographic variables (Table 1).
Using a freshly prepared mixture of propofol 1%/lidocaine 1% in a 10:1 ratio did not significantly affect the dose of propofol or time required to induce anesthesia compared with giving propofol as a separate injection after lidocaine (Table 2).
A larger proportion of patients in Group M were pain free compared with those in Group S (74.3% versus 50.0%) but the difference in pain scores did not reach statistical significance (P = 0.064) (Fig. 1).
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Figure 1. Pain on injection of propofol. Difference in pain scores between the two groups is not statistically significant (P = 0.064).
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Discussion
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Mixing lidocaine with propofol reduces the pain associated with injection of propofol in a dose-dependent manner (5,7).
Lilley et al. (11) showed that adding lidocaine to propofol emulsion increased the lipid droplet size and caused an oil droplet to form in a time- and dose-dependent manner. The propofol/lidocaine ratios used in the study ranged from 200:10 to 200:50 mg, similar to ratios used in clinical practice to reduce the pain of propofol injection (4,7,10). The addition of 10 mg of lidocaine to 90 mg of propofol also caused a time-dependent reduction of propofol concentration in the emulsion as propofol separated out to form an oily layer (15). Despite these changes, Lilley et al. (11) suggested that the changes in droplet size with freshly prepared mixtures using up to 20 mg of lidocaine to 200 mg of propofol were unlikely to have clinically significant effects. This is supported by the results of our study.
In contrast to our findings, two other studies suggested a decrease in anesthetic potency of propofol when administered as a propofol/lidocaine mixture. Eriksson et al. (12) found that mixing 20 mg of lidocaine with 200 mg of propofol increased the dose of propofol required to induce hypnosis in rats by 64%–68%.
Another study, looking at pain reduction with the addition of lidocaine and/or prilocaine to propofol in women undergoing dilation and curettage, showed a 34% increase in the total amount of propofol required to induce and maintain anesthesia in those who received a propofol/lidocaine mixture compared with those who received a propofol/saline mixture (8). The study compared the total doses of propofol, not induction doses or doses per kilogram of body weight. Although the mean duration of surgery and body weight were similar between the two groups, the actual figures were not stated, making comparisons with our study difficult. In this study, the control group received a propofol/saline mixture without lidocaine pretreatment whereas our control group received pretreatment with lidocaine. However, we do not expect the small dose of lidocaine we used (0.2 mg/kg) to affect the dose of propofol required to induce anesthesia because IM lidocaine 0.5 mg/kg and IV lidocaine 1.5 mg/kg did not change the dose of propofol needed for the induction of anesthesia (16,17).
We did not include a placebo group that did not have any lidocaine administered because our aim was to compare the induction doses of two clinical practices. Propofol is rarely given without lidocaine or analgesia in clinical practice because of the frequent incidence of pain reported with propofol injection.
Although studies have suggested that generic preparations of propofol may be associated with less pain on injection than DiprivanTM (18,19), the incidence of pain on injection of Abbott’s propofol has been reported to be similar to DiprivanTM (20). In the absence of a placebo group, the exact efficacy of the two methods for pain prevention could not be determined. Pain reduction, however, was not the main focus of this study. The lack of statistical significance of the decreased incidence and severity of pain in patients who received a propofol/lidocaine mixture could be attributable to inadequate sample size. Studies, including a quantitative review, comparing the efficacy of these two methods in reducing pain of propofol injection have had different conclusions (1,3,4).
In conclusion, the use of a freshly prepared mixture of propofol 1%/lidocaine 1% in a 10:1 volume ratio did not affect the dose of propofol required for the induction of anesthesia. The clinical effects of changes in propofol/lidocaine mixtures prepared in advance or with a larger proportion of lidocaine should be further investigated, because such situations do arise in clinical practice.
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Accepted for publication February 26, 2003.
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Abstract
Introduction
