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Year : 2017  |  Volume : 31  |  Issue : 2  |  Page : 123-126

Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain

Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India

Date of Web Publication20-Apr-2017

Correspondence Address:
Longjam Eshori
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-4958.204820

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Background: Propofol injection pain is one of the significant drawbacks to its use as an intravenous (IV) anesthetic induction agent so this study has been undertaken to compare the efficacy of IV acetaminophen and lidocaine on propofol injection pain. Materials and Methods: After obtaining Institutional Ethical Committee approval, ninety adult patients of ages 18–60 years of both sexes and American Society of Anaesthesiologist I and II who underwent elective surgery from September 2013 to September 2015 in the Tertiary Care Hospital, Imphal, were randomly allocated to one of the three groups to receive 10 ml saline (Group 1), 40 mg lidocaine (loxicard) in 10 ml saline (Group 2) and acetaminophen 100 mg (10 ml) (Group 3) to compare the pain efficacy during propofol injection into the large dorsal vein on the left hand. Pain was assessed with a verbal rating scale. Results: It was observed that the number of patients experiencing pain was 20 (66.67%), i.e., mild: moderate: severe - 11 (36.67%): 6 (20%): 3 (10%) in Group 1, in Group 2 the incidence was 2 (6.67%) i.e., mild: moderate: severe - 2 (6.67%): 0: 0, and in Group 3 it was 6 (20%) i.e., mild: moderate: severe - 5 (16.67%): 1 (3.33%): 0, respectively (P < 0.001). Conclusion: IV acetaminophen and lidocaine could significantly reduce pain during propofol injection with a significant P< 0.001.

Keywords: Acetaminophen, injection pain, lidocaine, propofol

How to cite this article:
Gangmei FL, Eshori L, Singh SS, Singh NR, Thapa M, Debbarman S. Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain. J Med Soc 2017;31:123-6

How to cite this URL:
Gangmei FL, Eshori L, Singh SS, Singh NR, Thapa M, Debbarman S. Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain. J Med Soc [serial online] 2017 [cited 2023 Jun 8];31:123-6. Available from:

  Introduction Top

Propofol (diprivan, di-isopropylphenol) is a popular intravenous (IV) anesthetic induction agent. However, very often it has the disadvantage of causing pain or discomfort on injection, especially when given in small vein on the dorsum of hand. This pain may be distressing to the patients and can reduce the acceptability of an otherwise useful agent. The incidence of pain varies between 28% and 90% in adults during induction of anesthesia [1] and in children the incidence of pain varies between 28% and 85%.[2]

Several methods have been proposed over the years in the literature to reduce the pain associated with IV injection of propofol. Recent attempts have been made to decrease this propofol-induced pain either with pharmacologic or nonpharmacologic method. The former comprise pretreatment with lidocaine,[3] ketamine,[4] thiopental,[5] metoclopramide,[6] or acetaminophen.[7]

Although the cause of propofol injection pain is unknown, the activation of pain mediators such as the release of a kininogen from the vein wall triggering a local kinin cascade system during IV injection has been suggested.[8]

Local anesthetics like loxicard have been shown to diminish prostaglandin synthesis and inhibit kinin cascade thereby reducing pain on injection of propofol.[8] The clinical effects of acetaminophen arise mostly from central action. Recently, it has demonstrated a weak peripheral effect by blocking impulse generation within the bradykinin sensitive chemoreceptors responsible for the generation of nociceptive impulses.[9]

The aim of the study was to evaluate the effectiveness of IV acetaminophen in comparison with that of lidocaine for the prevention of propofol-induced pain during induction of anesthesia.

  Materials and Methods Top

The study was randomized, double-blinded, placebo-controlled clinical trial with three arms carried out in the Department of Anaesthesiology, Tertiary Care Hospital, Imphal, Manipur, during 2 years starting from September 2013 to September 2015 on patients undergoing general anesthesia fulfilling the inclusion criteria were enrolled.

Inclusion criteria

Patients with American Society of Anaesthesiologist (ASA) I and II, aged between 18 and 60 years of both sexes coming for elective surgical procedure under general anesthesia were included in the study.

Exclusion criteria

Patients with a history of hypersensitivity to the study drug, pregnant and lactating mothers, anticipated difficult intubation and hemodynamically compromised, and patients' refusal were excluded from the study.

After the Institutional Ethical Committee approval and written informed consent were obtained. They were enrolled and explained about the purpose and procedure of the study. A preanesthetic evaluation was done in patients scheduled for elective general anesthesia. Detailed history, physical examination, and basic investigations were performed in all patients.

Patients on arrival in the operating room were preloaded with lactated Ringer's solution at 100 ml/h using a 20 gauge catheter into the large dorsal vein on the left hand. All patients were monitored with routine monitoring devices such as electrocardiograph, pulse oximetry (SpO2), and noninvasive blood pressure. All the patients planned for surgery received ranitidine 50 mg IV and glycopyrrolate 0.005 mg/kg intramuscular 1 h before surgery. An independent anesthetist prepared the solution and the investigator who was blinded to the content of the solutions conducted the study. After occluding the venous drainage using a pneumatic tourniquet (pressure inflated to 70 mmHg) on the upper arm, the patients were pretreated over a period of 10 s with one of the pretreatment solutions; 10 ml of normal saline (Group 1), 40 mg lidocaine (loxicard) in 10 ml saline (Group 2), and 10 ml of acetaminophen (paraglan IV) 100 mg (Group 3). After 2 min, the occlusion was released and one-fourth of the total calculated dose of propofol (2.5 mg/kg propofol-lipuro 1%) was delivered through the IV line over a period of 5 s. The pain that occurred during propofol injection was assessed on a 4-point verbal rating scale.[10]

  • 0 - None (negative response to question)
  • 1 - Mild pain (pain reported only in response to question without any behavioral sign)
  • 2 - Moderate pain (pain is reported in response to question and accompanied by behavioral sign and pain reported spontaneously without question)
  • 3 - Severe pain (strong vocal response or response accompanied by facial grimacing, arm withdrawal and tears).

Thereafter, induction of anesthesia continued and completed by injecting the remaining dose of propofol and endotracheal intubation was facilitated with neuromuscular blocking agents and maintained on with oxygen, nitrous oxide, inhalational agents, and muscle relaxant.

The data collected were entered on Excel spreadsheet after coding. The data were further processed and analyzed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) Windows-based version 21.0. Patient's characteristics were analyzed by Chi-square test and one-way analysis of variance (ANOVA). The Tukey's test was used for post hoc comparison and P< 0.05 was considered statistically significant.

  Results Top

There was no statistically significant difference in the demographic data (age, weight, height, sex, and ASA) among three groups on comparing them using ANOVA or F value and Chi-square test as shown in [Table 1].
Table 1: Demographic profile among three groups

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[Table 2] shows the distribution of the pain in the three groups during the first one-fourth propofol injection. The numbers of patients with no pain were 10 (33.33%) in Group 1, 28 (93.33%) in Group 2, and 24 (80%) in Group 3. Pain during injection was experienced by twenty (66.67%) patients in Group 1 followed by two (6.67%) and six (20%) patients in Group 2 and 3, respectively. These distributions of pain grades were statistically significant with a statistically F = 20.19 and a P< 0.001.
Table 2: The distribution of pain during propofol injection among the patients in the three groups

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Post hoc analysis using Tukey's test shows the intergroup comparison of pain during propofol injection in the three groups in [Table 3].
Table 3: The intergroup comparison of pain grades in the three groups

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In comparing Group 1 and 2, the number of patients with pain was 20 (66.67%) and 2 (6.67%) in Group 1 and 2, respectively. P value was found to be significant (<0.001).

The comparison of number of patients with pain between Group 1 and 3 was 20 (66.67%) versus 6 (20%), respectively, which was statistically significant (P < 0.001). In comparing Group 2 and 3, there was pain in two (6.67%) patients in Group 2 and six (20%) in Group 3 on injection of propofol with a P= 0.586 which was not significant.

  Discussion Top

Propofol is one of the most widely used IV induction agents, and one of the drawbacks of its use is the pain on injection. The mechanism of the pain is not well understood; propofol is known to irritate the skin, mucous membrane, and venous intima.[11] By an indirect action on the endothelium, it also activates the kallikrein-kinin system, thereby producing venous dilation and hyperpermeability, increasing the contact between propofol and the free nerve endings.[12]

In our study, the number of patients who experience pain on IV injection of propofol was 66.67% in the normal saline group as compared to 6.67% and 20% in the lidocaine and acetaminophen groups, respectively.

Lidocaine can be used as a pretreatment to alleviate propofol injection pain by acting as a local anesthetic. In our study, the incidence of pain of propofol injection on lidocaine group was 6.67% which is almost comparable with the work done by workers like Canbay et al.[7] who reported it to be 8%. Using a tourniquet allowed more contact time between lidocaine and the peripheral nerve endings thereby reducing the pain of propofol injection. Propofol activation of the kallikrein-kinin system and subsequent release of bradykinin was also reduced by the prior administration of lidocaine. Similar studies were conducted by Sasaki et al.[13] and Mangar and Holak [14] and they noted that there was increased analgesic effect of pre-injected lidocaine when a tourniquet was used concomitantly.

In another study conducted by Khouadja et al.,[15] the incidence of pain of propofol on lidocaine group was reported as 21.7% which is different from our study (6.67%). This could be due to the difference in sample size (150 vs. 90) and injection time (20 s vs. 5 s).

In our study, the incidence of pain during IV injection of propofol was 20% in the acetaminophen group which is almost comparable to the study conducted by Canbay et al.[7] of 22%. However, the authors used 50 mg of acetaminophen. Although the exact mechanism of action of acetaminophen analgesia is not clear, but recently it has been demonstrated that its acts peripherally by blocking impulse generation within the bradykinin sensitive chemoreceptors.[9]

In another study conducted by Khouadja et al.,[15] they found that the incidence of pain on injection of propofol in acetaminophen groups was 36% which is different from our study (20%). This could be due to different in the sample size and duration of injection.

Again in another study conducted by Ozkan et al.,[16] the incidence of pain reported in lidocaine and acetaminophen group was 25% and 10%, respectively, which is different from our findings as 6.67% in lidocaine group and 20% in acetaminophen group. This could be due to the difference in sample size (160 vs. 90) and tourniquet pressure (100 mmHg vs. 70 mmHg). However, they concluded that acetaminophen pretreatment with tourniquet was more effective than without tourniquet in preventing pain on injection.

In our study, we observed that a pretreatment with acetaminophen 100 mg and lidocaine 40 mg with a tourniquet duration of 120 s significantly reduced pain on injection of propofol when compared with a control (P < 0.001) group but we did not find any significant difference between 100 mg acetaminophen and 40 mg lidocaine (P = 0.586) in the severity of propofol-induced pain.

  Conclusion Top

From this study, it can be concluded that pretreatment with IV acetaminophen of 100 mg with venous occlusion for 2 min is effective as IV lidocaine (40 mg) to reduce pain induced by propofol injection, when compared to normal saline and may be used as an alternative to lidocaine.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Stark RD, Binks SM, Dutka VN, O'Connor KM, Arnstein MJ, Glen JB. A review of the safety and tolerance of propofol (Diprivan). Postgrad Med J 1985;61 Suppl 3:152-6.  Back to cited text no. 1
Valtonen M, Iisalo E, Kanto J, Tikkanen J. Comparison between propofol and thiopentone for induction of anaesthesia in children. Anaesthesia 1988;43:696-9.  Back to cited text no. 2
Picard P, Tramèr MR. Prevention of pain on injection with propofol: A quantitative systematic review. Anesth Analg 2000;90:963-9.  Back to cited text no. 3
Ugur B, Erpek G, Aydm ON. The effects of subanesthetic dose of ketamine on pain and hemodynamic changes after propofol injection. Turk Klin J Anesthesiol Reanim 2005;3:59-65.  Back to cited text no. 4
Agarwal A, Ansari MF, Gupta D, Pandey R, Raza M, Singh PK, et al. Pretreatment with thiopental for prevention of pain associated with propofol injection. Anesth Analg 2004;98:683-6.  Back to cited text no. 5
Fujii Y, Itakura M. Comparison of lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patients: A prospective, randomized, double-blind, parallel-group, placebo-controlled study. Clin Ther 2008;30:280-6.  Back to cited text no. 6
Canbay O, Celebi N, Arun O, Karagöz AH, Saricaoglu F, Ozgen S. Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain. Br J Anaesth 2008;100:95-8.  Back to cited text no. 7
Yull DN, Barkshire KF, Dexter T. Pretreatment with ketorolac and venous occlusion to reduce pain on injection of propofol. Anaesthesia 2000;55:284-7.  Back to cited text no. 8
Anderson BJ. Paracetamol (acetaminophen): Mechanisms of action. Paediatr Anaesth 2008;18:915-21.  Back to cited text no. 9
McCrirrick A, Hunter S. Pain on injection of propofol: The effect of injectate temperature. Anaesthesia 1990;45:443-4.  Back to cited text no. 10
Sun NC, Wong AY, Irwin MG. A comparison of pain on intravenous injection between two preparations of propofol. Anesth Analg 2005;101:675-8.  Back to cited text no. 11
Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: Review of clinical and experimental evidence. Pain 1993;52:259-85.  Back to cited text no. 12
Sasaki T, Okamura S, Kisara A, Ito M, Yogosawa K, Yagishita Y, et al. Effect of lidocaine on pain caused by injection of propofol: Comparison of three methods at two injection rates. J Anesth 1999;13:14-6.  Back to cited text no. 13
Mangar D, Holak EJ. Tourniquet at 50 mm Hg followed by intravenous lidocaine diminishes hand pain associated with propofol injection. Anesth Analg 1992;74:250-2.  Back to cited text no. 14
Khouadja H, Arnous H, Tarmiz K, Beletaifa D, Brahim A, Brahem W, et al. Pain on injection of propofol: Efficacy of paracetamol and lidocaine. Open J Anesthesiol 2014;4:81-7.  Back to cited text no. 15
Ozkan S, Sen H, Sizlan A, Yanarates O, Mutlu M, Dagli G. Comparison of acetaminophen (with or without tourniquet) and lidocaine in propofol injection pain. Bull Clin Psychopharmacol 2011;21:100-4.  Back to cited text no. 16


  [Table 1], [Table 2], [Table 3]


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