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* From the Department of Anaesthetics, Monash Medical Centre, Victoria, Australia;
and the Department of Anesthesiology, Childrens’ Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Address correspondence to: Dr. Terence Beh, Department of Anaesthetics, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia. Phone: 613-95943283; Fax: 613-95946290; E-mail: t.beh{at}southernhealth.org.au
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Abstract |
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Methods: Healthy children undergoing iv induction of general anesthesia for elective surgery were recruited into this prospective, randomized, double-blind study. None of the patients received any premedication except for eutectic mixture of local anesthetics cream. Before induction of anesthesia with propofol 1% mixed with lidocaine 0.05% (propofol dose 3 mg•kg-1), the treatment group received 50% N2O in O2 and the control group received 100% oxygen. Pain due to propofol administration was rated with a four-point behavioural scale: none, mild, moderate or severe.
Results: There were 28 subjects in the control group and 26 subjects in the treatment group. Demographic data were similar in both groups. The incidence of pain at induction was 4% after N2O and 36% in the control group, P < 0.01. No patients had severe pain. Most patients had mild pain. Three of the ten patients with pain in the control group had moderate pain. The number needed to treat was 3:1.
Conclusion: Nitrous oxide reduces pain during induction with propofol mixed with lidocaine in healthy children.
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Methods |
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Anesthetic management
Eutectic mixture of local anesthetics (EMLA) cream was applied to the dorsum of both hands at least one hour before scheduled operation time. No other premedications were given. Upon arrival at the operating room, an iv cannula of 22 or 24 gauge was placed in the dorsum of the subject’s hand. A circle system with fresh gas flow of 300 mL•kg-1•min-1 was used for administering the gases. The circuit was primed for 30 sec before use.
Subjects were randomized into two groups, by using a computer generated randomization table: Group A (treatment group) had O2 and N2O in equal ratios for two minutes before injection of propofol with 0.05% lidocaine; Group B (control group) had 100% O2 for two minutes before injection of propofol with 0.05% lidocaine.
Propofol with 0.05% lidocaine was prepared by mixing 0.5 mL of 1% lidocaine with 9.5 mL of propofol, to a total of 10 mL. This was done within half an hour of use. 3 mg•kg-1 of propofol were used for induction. Study gases were administered with a face mask gently held on the subject’s face but with an effective seal. The subject was blinded to the gases administered. Propofol was injected rapidly over 20 sec after the gases were given over two minutes. An independent rater blinded to the gases administered, rated pain of propofol administration with the four-point behavioural pain scale proposed by Cameron et al.:2 0 = no pain; 1 = mild pain (grimace); 2 = moderate pain (grimace + cry); and 3 = severe pain (cry + withdrawal).
Statistical analysis
Demographic data, such as age, sex, duration of gas administration, propofol injection time, incidence and severity of pain, were analyzed with Chi-square test, Mann-Whitney U test and Student’s t test. For alpha and beta values of 0.05 and 0.2 respectively, and predicting that the intervention would reduce the incidence of pain due to propofol administration by 20%, the sample size calculated was 54 subjects.
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Results |
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). There was a statistically significant difference in the incidence of pain between the two groups (P < 0.01). One (4%) out of 26 subjects in the nitrous oxide group had mild pain. Ten (36%) of the 28 subjects in the control group had pain. Of these, seven subjects had mild pain and three had moderate pain. None of the subjects had severe pain. The number needed to treat was 3:1, i.e., three subjects had to be treated to prevent pain in one subject.
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Discussion |
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N2O is a centrally-acting sedative and analgesic agent. It is perhaps not surprising that it should reduce the pain due to propofol injection. N2O has been used for iv cannulation in children10,11 and for other short painful procedures both in and outside operating rooms in hospitals.12,13 High concentration of N20 such as 70%, may cause side effects such as excitement, dysphoria, nausea, restlessness and opisthotonic movements,10 explaining why we chose to use a concentration of 50%. N2O is widely available and easy to administer. It is inexpensive and relatively free from side effects. At the same time as giving N2O, 50% of oxygen is also given to the patients. Hence there is some ‘preoxygenation’. It may have been possible that a fresh gas flow of 300 mL•kg-1•min-1 was inadequate to ensure that all subjects were breathing 50% N2O, because the minute volume at increased respiratory rates could exceed this flow rate. In this case, it was more likely that less than 50% of N2O was administered. So, although this remains a limitation of the study, it should further strengthen our conclusions.
All the subjects in this study had propofol with 0.05% lidocaine. Thirty-six percent of the control group had pain due to propofol injection. This figure is similar to that in adult subjects who received propofol with 0.05% lidocaine in the studies by King and Gajraj.5,7
In the course of the study, we had to exclude nine recruited patients because of failure to establish iv access. This is a fairly high failure rate and was possibly due to the vasoconstrictive effect of EMLA cream. We used EMLA cream as it was used in previous studies on propofol injection pain.2,9 EMLA cream does not appear to affect the incidence of propofol injection pain but this issue remains unclear. The use of amethocaine gel, which is vasodilating, would have introduced another variable and rendered comparisons with similar studies more difficult.
Assessing pain in children is often difficult and some sort of behavioural or biological method must be used. We chose to use the scale devised by Cameron et al.2,14 because it had been used for similar studies.
In conclusion, 50% nitrous oxide markedly reduces the pain due to the administration of a propofol-lidocaine admixture in healthy children. There was a fairly high incidence of pain in the control group although the pain was only mild to moderate.
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Acknowledgments |
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Footnotes |
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Revision received August 26, 2002. Accepted for publication April 29, 2002.
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2 Cameron E, Johnston G, Crofts S, Morton NS. The minimum effective dose of lignocaine to prevent injection pain due to propofol in children. Anaesthesia 1992; 47: 604–6.[Medline]
3 Picard P, Tramer MR. Prevention of pain on injection with propofol: a quantitative systematic review. Anesth Analg 2000; 90: 963–9.
4 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.[Medline]
5 King SY, Davis FM, Wells JE, Murchison DJ, Pryor PJ. Lidocaine for the prevention of pain due to injection of propofol. Anesth Analg 1992; 74: 246–9.[Medline]
6 Johnson RA, Harper NJN, Chadwick S, Vohra A. Pain on injection of propofol. Methods of alleviation. Anaesthesia 1990; 45: 439–42.[Medline]
7 Gajraj NM, Nathanson MH. Preventing pain during injection of propofol: the optimal dose of lidocaine. J Clin Anesth 1996; 8: 575–7.[Medline]
8 Ho CM, Tsou MY, Sun MS, Chu CC, Lee TY. The optimal effective concentration of lidocaine to reduce pain on injection of propofol. J Clin Anesth 1999; 11: 296–300.[Medline]
9 Valtonen M, Iisalo E, Kanto J, Rosenberg P. Propofol as an induction agent in children: pain on injection and pharmocokinetics. Acta Anaesthesiol Scand 1989; 33: 152–5.[Medline]
10 Henderson JM, Spence DG, Komocar LM, Bonn GE, Stenstrom RJ. Administration of nitrous oxide to pediatric patients provides analgesia for venous cannulation. Anesthesiology 1990; 72: 269–71.[Medline]
11 Vetter TR. A comparison of EMLA cream versus nitrous oxide for pediatric venous cannulation. J Clin Anesth 1995; 7: 486–90.[Medline]
12 Burton JH, Auble TE, Fuchs SM. Effectiveness of 50% nitrous oxide/50% oxygen during laceration repair in children. Acad Emerg Med 1998; 5: 112–7.[Medline]
13 Annequin D, Carbajal R, Chauvin P, Gall O, Tourniare B, Murat I. Fixed 50% nitrous oxide oxygen mixture for painful procedures: a French survey. Pediatrics 2000; 105: E47.
14 Pickford A, Burden J, Lewis I. Propofol and pain on induction: the effect of injectate temperature in children. Paediatr Anaesth 2000; 10: 129–32.[Medline]
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  R. G. Cox Are children just little adults when it comes to propofol injection pain?/Les enfants ne sont-ils que de jeunes adultes face a la douleur caus'e par l'injection de propofol ? Can J Anesth, December 1, 2002; 49(10): 1016 - 1020. [Full Text] [PDF]
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