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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094

Rev. Bras. Anestesiol. vol.51 no.5 Campinas Sept./Oct. 2001 



Pain after propofol intravenous injection in children: effects of combined lidocaine and inhalational nitrous oxide*


Dolor en la inyección venosa de propofol en niños: efectos de la adición de lidocaína y de la inhalación de óxido nitroso



Artur Udelsmann, TSA, M.D.I; Waston V Silva, M.D.II; Virgínia Maia da Conceição, M.D.II; Rosa Inês Costa Pereira, TSA, M.D.I

IProfessor (a) Doutor (a) de Departamento de Anestesiologia da FCM - UNICAMP





BACKGROUND AND OBJECTIVES: Hospital settings are stressful and fearful for children. Intravenous injections are mostly feared, especially if painful. Propofol is widely used for anesthesia induction but has the disadvantage of pain. This study aimed to compare two analgesic methods for intravenous propofol injection in children.
METHODS: Participated in this study 69 pediatric patients admitted for routine procedures under general anesthesia, with an intravenous line on the back of one hand, who were randomly allocated into four groups. Group 1 received previous inhalational O2 for 2 minutes and anesthesia was induced with propofol only. Group 2 inhaled O2 and to each 90 mg of propofol 10 mg of 1% lidocaine were added. Group 3 inhaled 66% N2O and 33% O2 and anesthesia was induced with propofol alone. Group 4 received a combination of both methods: children inhaled 66% N2O with 33% O2 and anesthesia was induced with propofol combined with lidocaine. Pain on induction and heart rate before and after injection were evaluated.
RESULTS: Group 4 was the only one with no changes in heart rate after propofol injection. Group 1 had more pain on induction and group 4 had less. Analgesia was insufficient for group 2, and group 3 has only shown a statistical trend to analgesia.
Conclusions: Dilution with lidocaine combined with N2O inhalation before intravenous propofol injection showed to be the most efficient method of analgesia for propofol induction in children.

Key words: ANESTHETICS, Inhalational: nitrous oxide; Local: lidocaine; ANESTHETIC TECHNIQUES, Intravenous: induction; HYPNOTICS: propofol


JUSTIFICATIVA Y OBJETIVOS: El medio hospitalario tiene varios factores de aprehensión y miedo para los niños. Entre ellos, las inyecciones venosas son uno de los más importantes factores, principalmente si dolorosas. El Propofol ha sido largamente utilizado para la inducción de la anestesia, más tiene el inconveniente de causar dolor en la inyección. El objetivo de este estudio fue comparar dos métodos de analgesia para la inyección venosa de propofol en niños.
MÉTODO: Sesenta y nueve niños admitidos al centro cirúrgico para procedimientos de rutina bajo anestesia general, previamente con una vía venosa instalada en el dorso de una de las manos, fueron aleatoriamente divididos en cuatro grupos. En el grupo 1, los niños inhalaran previamente, durante 2 minutos, O2 y la inducción fue hecha solamente con propofol. En el grupo 2, inhalaran O2 y a cada 90 mg de propofol fueron acrecentados 10 mg de lidocaína en la forma de solución a 1%. En el grupo 3, los niños inhalaran N2O 66% y O2 33% y el propofol fue usado puro. En el grupo 4, los dos métodos fueron combinados: los niños inhalaran N2O 66% con O2 33% y la inducción fue hecha con propofol diluido con lidocaína. El dolor en la inducción fue evaluado, así como la frecuencia cardíaca antes y después de la inyección.
RESULTADOS: El grupo 4 fue el único en el cual no se observó alteración de la frecuencia cardíaca después de la inyección de propofol. En el grupo 1, los niños presentaron más dolor y en el grupo 4 tuvieron menos dolor. En el grupo 2, la analgesia no fue suficiente y en el grupo 3 hubo solamente una tendencia estadística a la analgesia.
CONCLUSIONES:  En las condiciones de este estudio la inhalación previa de N2O antes de la inyección venosa de propofol asociado a la lidocaína mostró que puede ser el método de analgesia más eficaz para la inducción de la anestesia general con propofol en niños.




Propofol is an intravenous hypnotic agent being widely used for general anesthesia both in adults and, more recently, in children. Its major characteristic is its short duration, making it particularly interesting for outpatient procedures. With the increased experience with its use, other characteristics were gradually being evidenced, such as the anti-emetic effect, especially in children 1,2, the possibility of its use for tracheal intubation without muscle relaxants 3 and the relief of spinal opioids-induced pruritus 4. In addition, it has been used as hypnosis maintenance agent during total venous anesthesia 5.

Its major drawback is injection pain 5,6 which is particularly undesirable in pediatric anesthesia. The literature shows a prevalence of intravenous propofol injection pain which varies from 28% to 85% 7,8. Some solutions have been proposed to minimize such inconvenience. Lidocaine is the most popular and may be intravenously injected before the agent 9, or diluted in the propofol solution 10-14. In this latter formulation, the minimum effective dose for children 15 would be 0.2 or twice the dose recommended for adults 16. Other proposals would be the previous administration of sub-hypnotic thiopental doses 17,18 or the previous use of opioids such as 15 µ alfentanil 14,19,20 or 2.5 µ fentanyl 20.

Nitrous oxide is a weak, inodorous anesthetic gas used in anesthesia since the last century. In non-hypoxic mixtures it is unable to induce hypnosis in healthy people, but its inhalation allows for Guedel's stage 1 anesthesia to be reached 21, reason why it has been successfully proposed for less painful procedures in children, such as venous puncture 22,23, but it has not been used yet for intravenous propofol injection analgesia.

This double blind study aimed to evaluate the effects of two analgesia methods for intravenous propofol injection in children: 1) addition of 10 mg of 1% lidocaine to every 90 mg propofol; 2) N2O inhalation, isolated or in combination.



After the Faculdade de Ciências Médicas, Universidade Estadual de Campinas Ethics Committee approval, participated in this study 69 children of both genders, aged 8 months to 15 years, physical status ASA I, II or III, submitted to routine surgical procedures. All children arrived at the operating room with a venous line on the back of one hand. After parents or guardians informed consent, children were premedicated with 0.5 oral midazolam until a maximum of 15 mg and were randomly distributed in four groups. Group 1 inhaled 100% O2 under mask for 2 minutes before induction with 2 intravenous propofol. Group 2 inhaled 100% O2 and was induced with the same propofol dose where 10 mg of 1% lidocaine without vasoconstrictor were diluted to obtain a solution of 1 mg lidocaine per ml (0.1%). Group 3 inhaled 66% N2O and 33 O2 for two minutes and anesthesia was induced with 2 propofol only. Group 4 received a combination of both methods, that is, previous 66% N2O and 33% O2 inhalation and anesthesia induction with propofol diluted in lidocaine. In the operating room, monitoring consisted of ECG, pulse oximetry and non-invasive blood pressure. Participated in this study an anesthesiologist and an ME3 specialist. The anesthesiologist knew the group to which the patient had been assigned, prepared the propofol syringe and, hiding the anesthesia machine's fluxometers, applied the mask for the inhalation of gases, which were not known by the second investigator who would induce anesthesia and evaluate patients' reactions.

Pain was evaluated according to a 4-point scale, where:

0 = lack of intravenous injection reaction - no pain;
1 = mild upper limb movement - minor pain;
2 = upper limb retraction - moderate pain;
3 = upper limb retraction and cry - severe pain.

Heart rate before induction and immediately after loss of eyelash reflex was also evaluated.

To check homogeneity among groups for age, weight and heart rate before induction, Kruskal-Wallis test was applied. Contingency tables and chi-square test for association and, when needed, Fisher's Exact test were used for gender and physical status. Co-variance analysis was applied to check heart rate evolution before and after injection. Pain results for all groups were compared by Fisher's Exact test and moderate or severe pain were considered unacceptable.



Groups were homogeneous as to age, weight, gender and physical status (Table I).

Heart rate results before and after induction are shown in table II and figure 1. There were no differences in heart rate before induction in all groups, but there has been a significant pain increase after propofol injection in groups 1, 2 and 3.

Pain evaluation results for all groups are shown in table III.

Table IV was built considering unacceptable moderate and severe pain.

Group 1 had the largest number of unacceptable cases. The isolated use of lidocaine or N2O had similar results, but their simultaneous use (Group 4) led to a significant number of no pain cases. When comparing each analgesia method to the group without analgesia, the following results were obtained: lidocaine diluted in propofol did not provide significant analgesia and this is opposed to what is found in the literature 10,11,13,14, being probably due to the small sample size. N2O inhalation (Group 3) has shown just a trend (p = 0.103) to satisfactory analgesia for intravenous propofol injection. The simultaneous use of propofol diluted with lidocaine and N2O inhalation (Group 4) provided a better quality analgesia (p < 0.01) for venous induction with a significant number of cases with no pain or minor pain, as compared to the group not receiving analgesia. If considering that heart rate increase is a painful reaction, results obtained in Group 4 are further confirmed by the absence of significant heart rate variations.



Many are the factors making anesthesia an aggressive act for children, among them the idea of an injection, moreover if painful! Pediatric patients are often submitted to more than one hospitalization and even if subsequent admissions are not to be submitted to anesthesia, all efforts should be made for hospitals and physicians not being seen as aggression and fear factors. Propofol has been shown to be a useful agent for venous anesthesia, but pain on injection is an inconvenient which should be maximally minimized. Pain on injection pathophysiology of this drug is not totally explained and several hypothesis have been raised, none of them duly proven to date. The drug is not hyperosmolar with a pH between 6 and 8.5. Some factors, however, have been proven to worsen propofol intravenous injection pain, namely the size of the vein, which should be as large as possible to reduce pain 5,24, the speed of injection because the slower the injection the more painful it will be 10 and agent's temperature 25, which will cause more pain if injected cold. Currently proposed methods for less invasive procedures 10-14,22,23 were not satisfactory by themselves in our study. However, the combination of N2O with lidocaine, acting in different pain perception sites, has provided adequate analgesia for most cases and such procedure, in our opinion, should be encouraged for propofol-induced general anesthesia in children.



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Correspondence to:
Dr. Artur Udelsmann
Address: Av. Prof. Atílio Martini, 213
ZIP: 13084-210 City: Campinas, Brazil

Submitted for publication December 7, 2000
Accepted for publication April 20, 2001



* Received from CET do Departamento de Anestesiologia da Faculdade de Ciências Médicas da UNICAMP, Campinas, SP

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