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Departments of Anesthesia and *Biostatistics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
Address correspondence and reprint requests to Dr. Anil Agarwal, Type IV/48, SGPGIMS, Lucknow 226 014, India. Address email to aagarwal{at}sgpgi.ac.in
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Abstract |
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IMPLICATIONS: Pain associated with IV injection of propofol is seen in 28%–90% patients. Pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg after manual venous occlusion for 1 min effectively attenuated pain associated with propofol injection. Thiopental 0.5 mg/kg was the most effective in prevention of propofol pain and can be used routinely.
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Introduction |
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Pretreatment with thiopental (100 mg) was more effective than lidocaine (20 mg) in reducing the incidence of propofol-induced pain (8). In another study, lidocaine 2% (40 mg) reduced the incidence and severity of propofol injection pain in ambulatory patients, whereas thiopental (50 mg) only reduced its severity (9). The effect of the thiopental pretreatment after venous occlusion for prevention of propofol-induced pain has not been studied. Duration of venous occlusion and the dose of lidocaine used was based on a meta-analysis that concluded that the optimal method for prevention of propofol-associated pain is to give IV lidocaine 0.5 mg/kg while a tourniquet is applied to the forearm for a period of 30–120 s before injection of propofol (7). We therefore evaluated the efficacy of lidocaine 2% (40 mg) for prevention of pain associated with propofol injection and compared its efficacy with that of small-dose thiopental pretreatment 0.25 mg/kg and 0.5 mg/kg after venous occlusion at the forearm, 1 min before injection of propofol.
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Methods |
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Assuming that the incidence of pain after IV propofol is 70% and that this would be reduced to 35% after therapy, power analysis with 
= 0.05, ß = 0.8 showed that we would need to study 31 patients in each group. The study therefore consisted of 124 consecutive patients, ASA physical status I–II, aged 18–50 yr, undergoing elective surgical procedures lasting between 1–2 h. Using a computer-generated table of random numbers, patients were assigned into 4 groups of 31 each. Patients in Group I (NS) received normal saline, Group II (L) received lidocaine 2% (40 mg), and Groups III (T25) and IV (T50) received thiopental 0.25 mg/kg and 0.5 mg/kg, respectively. All study drugs were made into 2 mL with NS and were administered over 5 s in a dedicated IV line (18-gauge) in a vein on the dorsum of the nondependent hand while the venous drainage was occluded manually at the middle of the forearm just before the administration of the study drug and was maintained for 1 min. Another cannula was placed in the vein on the dorsum of the other hand for the infusion of IV fluids. Patients then received 1/4 of the total calculated dose of propofol over 5 s. The induction dose of propofol (Propofol 1% W/V in lipid base; Claris Lifesciences Limited, Ahmedabad, India) was 2.5 mg/kg. All study drugs were kept at room temperature and used within 30 min of preparation.
During the propofol injection, patients were continuously observed for vocal response, facial grimacing, arm withdrawal, or tears suggesting severe pain. If these signs and symptoms were absent then patients were questioned every 5–10 s during induction regarding the presence of pain or discomfort. Pain was graded using a four-point scale: 0 = no pain, 1 = mild pain (pain reported only in response to questioning without any behavioral signs), 2 = moderate pain (pain reported in response to questioning and accompanied by a behavioral sign or pain reported spontaneously without questioning), and 3 = severe pain (i.e., strong vocal response or response accompanied by facial grimacing, arm withdrawal, or tears) (10).
Patients were given oral lorazepam 2 mg and ranitidine 150 mg the night before surgery and 2 h before the induction of anesthesia. Monitoring consisted of electrocardiogram, noninvasive arterial blood pressure, and pulse oximetry. An anesthesiologist not involved in the study prepared pretreatment drugs. The remaining dose of propofol was administered slowly after assessment of pain. Fentanyl was administered only after induction of anesthesia. A second, independent anesthesiologist who was unaware of group assignments, assessed the level of pain. Within 24 h after operation, the injection site was checked for pain, edema, wheal, and flare response by an anesthesiologist who was unaware which drug was administered. Results were analyzed by comparing two proportions by normal approximation ("Z" test). When the distribution of data regarding grading of pain was not normal, Fisher’s exact test was applied. The package SPSS 9.0 (SPSS, Chicago, IL) was used for statistical analysis. P 
0.05 was considered as significant.
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Results |
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Discussion |
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Propofol belongs to the group of phenols that can irritate the skin, mucous membranes, and venous intima (11). Propofol, by an indirect action on the endothelium, activates the kallikrein-kinin system and releases bradykinin, thereby producing venous dilation and hyperpermeability, which increases the contact between the aqueous phase of propofol and free nerve endings, resulting in pain on injection (4,12). Propofol, when drawn up in a disposable syringe, may lead to formation of irritants and propofol pain (13). It has been confirmed that propofol strips the silicone lubricant from the inside barrel of plastic syringes. A reduction in propofol pain by cooling it to 4°C (6) and diluting the propofol (14) may slow or prevent this reaction between propofol and plastic.
The mechanism by which thiopental reduces pain on injection of propofol is unknown. However, it could be either because of any or all of the following reasons. First, the physical properties of thiopental such as its alkalinity or lipid solubility may affect the concentration of free aqueous propofol, which is responsible for propofol pain (15). Second, co-administration of subanesthetic doses of thiopental and propofol may inhibit the perception of pain (16). Finally, thiopental may exert its effect by preventing the release bradykinin, which causes venous dilation and hyperpermeability and thus increases the contact between the aqueous phase of propofol and free nerve endings, resulting in pain on propofol injection (4).
Various methods have been used for attenuating pain during IV injection of propofol such as using larger veins, decreasing speed of injection, injecting propofol into a fast-running I/V fluid, diluting it with 5% glucose or 10% intralipid, prior injection of lidocaine, alfentanil, fentanyl, or thiopental, injecting cold saline at 4°C before propofol, and mixing lidocaine in propofol and cooling propofol to 4°C (4–6,17,18).
Lee et al. (8) reported that pretreatment with 100 mg thiopental (1.6 mg/kg based on average weight of patients) attenuated propofol pain when compared with lidocaine 20 mg. Nevertheless the sedative effect of such a large dose of thiopental on perception of pain as assessed by visual analog scale cannot be eliminated. Haugen et al. (9) compared the efficacy of thiopental 50 mg (approximately 0.8 mg/kg) pretreatment with lidocaine 40 mg and observed that thiopental only reduced the severity of propofol pain, whereas lidocaine reduced both the incidence and severity of pain. We administered comparatively smaller doses of thiopental (0.25 mg/kg and 0.5 mg/kg) and observed effective attenuation of propofol pain. Thiopental in these doses is unlikely to alter pain perception. The difference in our results from those of the earlier studies could be because of the difference in the technique of administering thiopental. We administered thiopental after venous occlusion that was released after 1 min. Duration of venous occlusion and the dose of lidocaine used was based on a meta-analysis that concluded that the optimal method for prevention of propofol associated pain is to give IV lidocaine 0.5 mg/kg while a tourniquet is applied to the forearm for a period of 30–120 s before injection of propofol (7). Therefore, thiopental may have had a better opportunity to act locally by preventing the release of bradykinin associated with injection of propofol and thus prevent propofol pain. However such an affirmation deserves closer investigation.
Minimizing propofol injection pain is an important clinical goal because it may influence the patient’s perception of quality and acceptability of anesthesia. In conclusion, pretreatment with lidocaine 40 mg, thiopental 0.25 mg/kg, and thiopentone 0.5 mg/kg after manual venous occlusion attenuates propofol pain. However, pretreatment with thiopental 0.5 mg/kg after manual venous occlusion was the most effective in attenuating propofol-induced pain. We therefore suggest routine pretreatment with thiopental 0.5 mg/kg along with manual venous occlusion for 1 min for prevention of pain associated with propofol injection.
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This article has been cited by other articles:
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  O. Canbay, N. Celebi, O. Arun, A. H. Karagoz, F. Saricaoglu, and S. Ozgen Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain Br. J. Anaesth., January 1, 2008; 100(1): 95 - 98. [Abstract] [Full Text] [PDF]
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 N. C. H. Sun, A. Y. C. Wong, and M. G. Irwin A Comparison of Pain on Intravenous Injection Between Two Preparations of Propofol Anesth. Analg., September 1, 2005; 101(3): 675 - 678. [Abstract] [Full Text] [PDF]
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T. Lacy, N. Roy Connelly, K. Freeman, A. Agarwal, M. F. Ansari, S. Dhiraaj, and M. Raza Don't Use Thiopental to Decrease Propofol Injection Pain * Response Anesth. Analg., September 1, 2004; 99(3): 953 - 954. [Full Text] [PDF]
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