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Published in: BMC Anesthesiology 1/2019

Open Access 01-12-2019 | Paracetamol | Research article

Premedication with oral paracetamol for reduction of propofol injection pain: a randomized placebo-controlled trial

Authors: Sasikaan Nimmaanrat, Manasanun Jongjidpranitarn, Sumidtra Prathep, Maliwan Oofuvong

Published in: BMC Anesthesiology | Issue 1/2019

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Abstract

Background

To compare the effect of premedication with 2 different doses of oral paracetamol to prevent pain at propofol intravenous injection.

Methods

We conducted a double-blind randomized controlled trial in which patients scheduled for induction of general anesthesia with intravenous propofol received either a placebo, 500 mg or 1000 mg of oral paracetamol (P500 and P1000, respectively) 1 h prior to induction. Two mg/kg of propofol was injected at a rate of 600 ml/hr. After 1/4 of the full dose had been injected, the syringe pump was paused, and patients were asked to rate pain at the injection site using a verbal numerical rating score (VNRS) from 0 to 10.

Results

Three hundred and twenty-four patients were included. Pain intensity was lower in both P500 and P1000 groups (median VNRS [interquartile range] = 2 [0–3] and 4 [2–5], respectively) than in the placebo group (8 [7–10]; P < 0.001)*. The rate of pain was lower in the P1000 group (70.4%) than in both the P500 and the placebo group (86.1 and 99.1%, respectively; P < 0.001)*. The respective rates of mild (VNRS 1–3), moderate (VNRS 4–6) and severe pain (VNRS 7–10) were 47.2, 23.2 and 0% in the P1000 group, 28.7, 50 and 7.4% in the P500 group, and 0, 22.2 and 76.9% in the placebo group (P < 0.001* for between group comparisons). Tolerance was similar in the 3 groups.

Conclusions

A premedication with oral paracetamol can dose-dependently reduce pain at propofol intravenous injection. To avoid this common uncomfortable concern for the patients, this well-tolerated, available and cheap treatment appears as an option to be implemented in the current practice.

Trial registration

TCTR20150224002. Prospectively registered on 24 February 2015.
Literature
1.
go back to reference Tan CH, Onsiong MK. Pain on injection of propofol. Anaesthesia. 1998;53:468–76.CrossRef Tan CH, Onsiong MK. Pain on injection of propofol. Anaesthesia. 1998;53:468–76.CrossRef
2.
go back to reference Stark RD, Binks SM, Dutka VN, O’Connor KM, Arnstein MJA, Glen JB. A review of the safety and tolerance of propofol (Diprivan). Postgrad Med J. 1985;61:152–6.PubMed Stark RD, Binks SM, Dutka VN, O’Connor KM, Arnstein MJA, Glen JB. A review of the safety and tolerance of propofol (Diprivan). Postgrad Med J. 1985;61:152–6.PubMed
3.
go back to reference Manger D, Holak EJ. Tourniquet at 50 mmHg followed by intravenous lidocaine diminishes hand pain associated with propofol injection. Anesth Analg. 1992;74:250–2.CrossRef Manger D, Holak EJ. Tourniquet at 50 mmHg followed by intravenous lidocaine diminishes hand pain associated with propofol injection. Anesth Analg. 1992;74:250–2.CrossRef
4.
go back to reference Klement W, Arndt JO. Pain on intravenous injection of some anaesthetic agents is evoked by the unphysiological osmolarity or pH of their formulations. Br J Anaesth. 1991;66:189–95.CrossRef Klement W, Arndt JO. Pain on intravenous injection of some anaesthetic agents is evoked by the unphysiological osmolarity or pH of their formulations. Br J Anaesth. 1991;66:189–95.CrossRef
5.
go back to reference Nakane M, Iwama H. A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate. Br J Anaesth. 1999;83:397–404.CrossRef Nakane M, Iwama H. A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate. Br J Anaesth. 1999;83:397–404.CrossRef
6.
go back to reference McCulloch MJ, Lees NW. Assessment and modification of pain on induction with propofol (Diprivan). Anaesthesia. 1985;40:1117–20.CrossRef McCulloch MJ, Lees NW. Assessment and modification of pain on induction with propofol (Diprivan). Anaesthesia. 1985;40:1117–20.CrossRef
7.
go back to reference Scott RPF, Saunders DA, Norman J. Propofol: clinical strategies for preventing pain on injection. Anaesthesia. 1988;43:492–4.CrossRef Scott RPF, Saunders DA, Norman J. Propofol: clinical strategies for preventing pain on injection. Anaesthesia. 1988;43:492–4.CrossRef
8.
go back to reference Briggs LP, Clarke RSJ, Dundee JW, Moore J, Bahar M, Wright PJ. Use of di-isopropyl phenol as main agent for short procedures. Br J Anaesth. 1981;53:1197–201.CrossRef Briggs LP, Clarke RSJ, Dundee JW, Moore J, Bahar M, Wright PJ. Use of di-isopropyl phenol as main agent for short procedures. Br J Anaesth. 1981;53:1197–201.CrossRef
9.
go back to reference Huang CL, Wang YP, Cheng YJ, Susetio L, Liu CC. The effect of carrier intravenous fluid speed on the injection pain of propofol. Anesth Analg. 1995;81:1087.PubMed Huang CL, Wang YP, Cheng YJ, Susetio L, Liu CC. The effect of carrier intravenous fluid speed on the injection pain of propofol. Anesth Analg. 1995;81:1087.PubMed
10.
go back to reference McDonald DS, Jameson P. Injection pain with propofol. Reduction with aspiration of blood. Anaesthesia. 1996;51:878–80.CrossRef McDonald DS, Jameson P. Injection pain with propofol. Reduction with aspiration of blood. Anaesthesia. 1996;51:878–80.CrossRef
11.
go back to reference Ganta R, Fee JP. Pain on injection of propofol: comparison of lignocaine with metoclopramide. Br J Anaesth. 1992;69:316–7.CrossRef Ganta R, Fee JP. Pain on injection of propofol: comparison of lignocaine with metoclopramide. Br J Anaesth. 1992;69:316–7.CrossRef
12.
go back to reference Kizilcik N, Menda F, Bilgen S, Keskin O, Koner O. Effects of a fentanyl-propofol mixture on propofol injection pain: a randomized clinical trial. Korean J Anesthesiol. 2015;68:556–60.CrossRef Kizilcik N, Menda F, Bilgen S, Keskin O, Koner O. Effects of a fentanyl-propofol mixture on propofol injection pain: a randomized clinical trial. Korean J Anesthesiol. 2015;68:556–60.CrossRef
13.
go back to reference Bahar M, McAteer E, Dundee JW, Briggs LP. Aspirin in the prevention of painful intravenous injection of disoprofol (ICI 35, 868) and diazepam (valium). Anaesthesia. 1982;37:847–8.CrossRef Bahar M, McAteer E, Dundee JW, Briggs LP. Aspirin in the prevention of painful intravenous injection of disoprofol (ICI 35, 868) and diazepam (valium). Anaesthesia. 1982;37:847–8.CrossRef
14.
go back to reference Jalota L, Kalira V, George E, Shi YY, Hornuss C, Radke O, et al. Prevention of pain on injection of propofol: systematic review and meta-analysis. Cited as. BMJ. 2011;342:d1110.CrossRef Jalota L, Kalira V, George E, Shi YY, Hornuss C, Radke O, et al. Prevention of pain on injection of propofol: systematic review and meta-analysis. Cited as. BMJ. 2011;342:d1110.CrossRef
15.
go back to reference Canbay O, Celebi N, Arun O, Karagoz H, Sarıcaoglu F, Ozgen S. Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain. Br J Anaesth. 2008;100:95–8.CrossRef Canbay O, Celebi N, Arun O, Karagoz H, Sarıcaoglu F, Ozgen S. Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain. Br J Anaesth. 2008;100:95–8.CrossRef
16.
go back to reference Borazan H, Erdem TB, Kececioglu M, Otelcioglu S. Prevention of pain on injection of propofol: a comparison of lidocaine with different doses of paracetamol. Eur J Anaesthesiol. 2010;27:253–7.CrossRef Borazan H, Erdem TB, Kececioglu M, Otelcioglu S. Prevention of pain on injection of propofol: a comparison of lidocaine with different doses of paracetamol. Eur J Anaesthesiol. 2010;27:253–7.CrossRef
17.
go back to reference Seymour RA, Kelly PJ, Hawkesford JE. The efficacy of ketoprofen and paracetamol (acetaminophen) in postoperative pain after third molar surgery. Br J Clin Pharmacol. 1996;41:581–5.CrossRef Seymour RA, Kelly PJ, Hawkesford JE. The efficacy of ketoprofen and paracetamol (acetaminophen) in postoperative pain after third molar surgery. Br J Clin Pharmacol. 1996;41:581–5.CrossRef
18.
go back to reference Jozwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications, and safety concern. Acta Pol Pharm. 2014;71:11–23.PubMed Jozwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications, and safety concern. Acta Pol Pharm. 2014;71:11–23.PubMed
19.
go back to reference Candido KD, Perozo OJ, Knezevic NN. Pharmacology of acetaminophen, nonsteroidal antiinflammatory drugs, and steroid medications: implications for anesthesia or unique associated risks. Anesthesiol Clin. 2017;35:e145–62.CrossRef Candido KD, Perozo OJ, Knezevic NN. Pharmacology of acetaminophen, nonsteroidal antiinflammatory drugs, and steroid medications: implications for anesthesia or unique associated risks. Anesthesiol Clin. 2017;35:e145–62.CrossRef
20.
go back to reference Graham GG, Scott KF. Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology. 2003;11:401–13.CrossRef Graham GG, Scott KF. Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology. 2003;11:401–13.CrossRef
21.
go back to reference Lee YS, Kim H, Brahim JS, Rowan J, Lee G, Dionne RA. Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain. 2007;129:279–86.CrossRef Lee YS, Kim H, Brahim JS, Rowan J, Lee G, Dionne RA. Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain. 2007;129:279–86.CrossRef
22.
go back to reference Mallet C, Barriera DA, Ermund A, Jonsson BAG, Eschalier A, Zygmunt PM, et al. TRPV1 in brain is involved in acetaminophen-induced antinociception. PLoS One. 2010;5:e12748.CrossRef Mallet C, Barriera DA, Ermund A, Jonsson BAG, Eschalier A, Zygmunt PM, et al. TRPV1 in brain is involved in acetaminophen-induced antinociception. PLoS One. 2010;5:e12748.CrossRef
23.
go back to reference Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, et al. Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain. 2008;139:190–200.CrossRef Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, et al. Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain. 2008;139:190–200.CrossRef
24.
go back to reference Pickering G, Esteve V, Loriot MA, Eschalier A, Dubray C. Acetaminophen reinforces descending inhibitory pain pathways. Clin Pharmacol Ther. 2008;84:47–51.CrossRef Pickering G, Esteve V, Loriot MA, Eschalier A, Dubray C. Acetaminophen reinforces descending inhibitory pain pathways. Clin Pharmacol Ther. 2008;84:47–51.CrossRef
25.
go back to reference Bonnefont J, Alloui A, Chapuy E, Clottes E, Eschalier A. Orally administered paracetamol does not act locally in the rat formalin test: evidence for a supraspinal, serotonin-dependent antinociceptive mechanism. Anesthesiology. 2003;99:976–81.CrossRef Bonnefont J, Alloui A, Chapuy E, Clottes E, Eschalier A. Orally administered paracetamol does not act locally in the rat formalin test: evidence for a supraspinal, serotonin-dependent antinociceptive mechanism. Anesthesiology. 2003;99:976–81.CrossRef
26.
go back to reference Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther. 2006;79:371–8.CrossRef Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther. 2006;79:371–8.CrossRef
27.
go back to reference Bjorkman R. Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol. Experimental studies in the rat. Acta Anaesthesiol Scand. 1995;103(Suppl.):1–44. Bjorkman R. Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol. Experimental studies in the rat. Acta Anaesthesiol Scand. 1995;103(Suppl.):1–44.
28.
go back to reference Bujalska M. Effect of nitric oxide synthase inhibitor on antinociceptive action of different doses of acetaminophen. Pol J Pharmacol. 2004;56:605–10.CrossRef Bujalska M. Effect of nitric oxide synthase inhibitor on antinociceptive action of different doses of acetaminophen. Pol J Pharmacol. 2004;56:605–10.CrossRef
29.
go back to reference Ohashi N, Uta D, Sasaki M, Ohashi M, Kamiya Y, Kohno T. Acetaminophen metabolite N-acylphenolamine induces analgesia via transient receptor potential vanilloid 1 receptors expressed on the primary afferent terminals of C-fibers in the spinal dorsal horn. Anesthesiology. 2017;127:355–71.CrossRef Ohashi N, Uta D, Sasaki M, Ohashi M, Kamiya Y, Kohno T. Acetaminophen metabolite N-acylphenolamine induces analgesia via transient receptor potential vanilloid 1 receptors expressed on the primary afferent terminals of C-fibers in the spinal dorsal horn. Anesthesiology. 2017;127:355–71.CrossRef
30.
go back to reference Janz DR, Bastarache JA, Rice TW, Bernard GR, Warren MA, Wickersham N, et al. Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the acetaminophen for the reduction of oxidative injury in severe Sepsis trial. Crit Care Med. 2015;43:534–41.CrossRef Janz DR, Bastarache JA, Rice TW, Bernard GR, Warren MA, Wickersham N, et al. Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the acetaminophen for the reduction of oxidative injury in severe Sepsis trial. Crit Care Med. 2015;43:534–41.CrossRef
31.
go back to reference 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.CrossRef 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.CrossRef
32.
go back to reference 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. Klinik Psikofarmakol Bülteni. 2011;21:100–4.CrossRef 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. Klinik Psikofarmakol Bülteni. 2011;21:100–4.CrossRef
33.
go back to reference Singla NK, Parulan C, Samson R, Hutchinson J, Bushnell R, Beja EG, et al. Plasma and cerebrospinal fluid pharmacokinetic parameters after single dose administration of intravenous, oral or rectal acetaminophen. Pain Pract. 2012;12:523–32.CrossRef Singla NK, Parulan C, Samson R, Hutchinson J, Bushnell R, Beja EG, et al. Plasma and cerebrospinal fluid pharmacokinetic parameters after single dose administration of intravenous, oral or rectal acetaminophen. Pain Pract. 2012;12:523–32.CrossRef
34.
go back to reference Fenlon S, Collyer J, Giles J, Bidd H, Lees M, Nicholson J, et al. Oral vs intravenous paracetamol for lower third molar extractions under general anaesthesia: is oral administration inferior? Br J Anaesth. 2013;110:432–7.CrossRef Fenlon S, Collyer J, Giles J, Bidd H, Lees M, Nicholson J, et al. Oral vs intravenous paracetamol for lower third molar extractions under general anaesthesia: is oral administration inferior? Br J Anaesth. 2013;110:432–7.CrossRef
35.
go back to reference Bendinger T, Plunkett N. Measurement in pain medicine. BJA Education. 2016;16:310–5.CrossRef Bendinger T, Plunkett N. Measurement in pain medicine. BJA Education. 2016;16:310–5.CrossRef
Metadata
Title
Premedication with oral paracetamol for reduction of propofol injection pain: a randomized placebo-controlled trial
Authors
Sasikaan Nimmaanrat
Manasanun Jongjidpranitarn
Sumidtra Prathep
Maliwan Oofuvong
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2019
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-019-0758-y

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