Tonsillectomy in children is a common operation. Although many observational studies have been conducted, relief of pain after the operation is still an unresolved problem . Anticipation of postoperative pain, separation from the family and fear of surgery trigger symptoms of perioperative anxiety. This in turn can produce aggressive reactions, which make the management of the patient difficult . Hence, in children it is very difficult to assess pain and in the postoperative care unit (PACU) restlessness and crying may be regarded as indicative of pain resulting from inadequate analgesia .
The provision of pre-emptive analgesia - defined as the administration of analgesic agents before an injury in order to prevent development of central nervous system hyperexcitability or sensitization - is currently of great interest. It is believed that central sensitization results from increased excitability of the dorsal horn neurons in the spinal cord and after such sensitization an exaggerated responsiveness to further noxious stimuli may ensue that may be associated with a decrease in the pain threshold . Therefore, administration of opioids, non-steroidal anti-inflammatory agents (NSAIDs) or local anaesthetics - together with premedication before induction of general anaesthesia - is common in our practice.
Tramadol is a centrally acting analgesic through opioid receptors. Its intravenous (i.v.) analgesic effect has been reported to be equal or one-half that of meperidine, and one-tenth that of morphine and nalbuphine, while exhibiting less sedation and absence of respiratory depression . Although many studies have documented the analgesic effects of tramadol and/or meperidine, their pre-emptive use for tonsillectomy pain management in children has been compared in only one study . In the present study, the perioperative analgesic and recovery characteristics of tramadol 3 mg kg−1 were compared with those of meperidine 1.5 mg kg−1. High perioperative doses of tramadol are questionable because of the risk of awareness; it has been suggested that 65% of patients complained of awareness during anaesthesia  when doses >200 mg were given i.v. to adults. We therefore compared the effects of equipotent lower doses of tramadol and meperidine on pain relief and characteristics in children undergoing tonsillectomy.
With the approval of our Faculty Ethics Committee, 50 children scheduled for tonsillectomy with or without adenoidectomy were included in the study. All children were ASA I-II and aged 4-7 yr. After induction of anaesthesia but before endotracheal intubation, children were randomized to receive either tramadol 1 mg kg−1 or meperidine 1 mg kg−1 i.v. over 30 s.
In all children, an eutectic mixture of local anaesthetic cream (EMLA) was applied 1 h before surgery to provide analgesia for the insertion of an i.v. cannula. Thirty minutes before the induction of anaesthesia, all patients were premedicated with midazolam 0.03 mg kg−1 i.v. After application of routine non-invasive monitoring devices (blood pressure, electrocardiogram, pulse oximeter, capnograph), anaesthesia was induced with propofol 2 mg kg−1 i.v.; cis-atracurium 0.15 mg kg−1 i.v. was given to facilitate endotracheal intubation. Anaesthesia was maintained with sevoflurane 1.5-2% in a mixture of N2O 50% and O2. Controlled ventilation of the lungs was applied at 12-14 breaths min−1 to maintain end-tidal carbon dioxide to between 4.7 and 5.3 kPa. At the end of surgery residual neuromuscular block was antagonized with neostigmine 0.05 mg kg−1 and atropine 0.015 mg kg−1 and the patient's lungs were ventilated with oxygen 100%. Extubation was performed when spontaneous breathing was adequate.
Heart rate and non-invasive mean arterial pressure were recorded: (a) before and (b) after induction of anaesthesia, (c) after tracheal intubation, (d) 15 min into the operation, and (e) at the end of surgery.
Postoperative agitation was assessed when the children arrived in the postanaesthesia care unit (PACU) (at 0 min) according to Davis and colleagues  by a three-point score (1 = asleep or calm; 2 = wildly agitated, crying but consolable, restless; 3 = hysterical, crying inconsolably). The nurse in the PACU who was unaware of the nature of the test drug assessed the agitation score. The same nurse evaluated analgesia by using the facial pain scale at 0, 10, 20 and 45 min . This scale contains seven faces that are assigned numerical values (0 = no pain (a smiling face), 6 = worst pain) (Fig. 1). In children presenting a facial pain score >5, acetaminophen (paracetamol) suppositories (20 mg kg−1) were administered at the 45th min. The time to recovery to spontaneous breathing and the incidence of nausea and vomiting were recorded for 45 min in the PACU.
Age, weight, duration of surgery and time to spontaneous respiration were compared between two groups using analysis of variance (ANOVA). The statistical differences between groups, gender and periods with respect to heart rate and mean arterial pressure were analysed by repeated measurement of ANOVA, and power analysis was performed for statistically important results. The Friedman test was used for comparison of pain (facial pain score) and agitation scores. Differences between the groups were analysed by the U-test. Results are expressed as the mean ± SD; P < 0.05 was considered as statistically significant.
There was no significant difference between the two groups with respect to age, body weight, gender and duration of surgery (Table 1). Heart rate and mean arterial pressures recorded at regular intervals were not significantly different between the two groups (Table 2). All children had adenotonsillectomy performed except for one child in the tramadol group and two children in the meperidine group who had tonsillectomy only. Facial pain scores were higher in the tramadol group at 0, 10 and 20 min (P < 0.05) (Table 3). On the other hand, no significant difference was observed in facial pain scores recorded at the 45 min in the PACU.
Agitation scores were higher in the tramadol group (2.1 ± 0.9) compared with the meperidine group (1.4 ± 0.7) (n.s.).
Recovery of spontaneous breathing after administration of neostigmine and atropine was delayed in the meperidine group (4.75 ± 2.51) compared with the tramadol group (3.00 ± 1.05) (P < 0.05). Treatment with naloxone was unnecessary. The incidence of nausea and vomiting was not significantly different between the two groups (2/25 in the tramadol group, 3/25 in the meperidine group).
Our data demonstrate that meperidine provided more effective analgesia and smoother emergence than tramadol in children undergoing tonsillectomy. Although recovery of spontaneous ventilation was delayed by 1-2 min at the end of anaesthesia in the meperidine group, restlessness and agitation were lessened.
The outcome and morbidity following tonsillectomy and subsequent parent and child anxiety at early discharge of prospective studies were higher than that had been expected . It has been reported that children who were more anxious in the preoperative period showed a threefold higher risk of a high anxiety level in the postoperative period and a high level of anxiety associated with greater pain sensation and agitation. However, a quiet pain-free recovery from anaesthesia is most desirable following adenotonsillectomy [9-11].
In our study, emergence and recovery were not as smooth as we had hoped for. These data in part may result from the rapid transition to consciousness - due to the anaesthetic regimen - as well as from insufficient analgesia after rapid emergence . In addition, we found that the agitation scores after tramadol were higher than after meperidine. This result was consistent with the study of van den Berg and colleagues who demonstrated a better postoperative emergence with meperidine than with tramadol. In this study, the perioperative analgesic and recovery characteristics of equipotent meperidine and tramadol were compared in children undergoing tonsillectomy and it was suggested that tramadol 3 mg kg−1, given with induction of anaesthesia, conferred little antinociceptive benefit and smooth emergence into the postoperative period . We assume that this is due to the analgesic effect of tramadol mediated by non-opioid receptor mechanisms. Tramadol does not have the advantage of opioid-induced sedation, which is highly desirable in the early postoperative period. More recently, in contrast to the findings of Van den Berg and colleagues, Özköse and colleagues presented different data for children undergoing tonsillectomy. In their study, tramadol 0.5 and 1 mg kg−1 was given before induction of anaesthesia and it was found that even the low dose of 0.5 mg kg−1 provided effective postoperative pain relief . However, our data conflict with the study of Özköse and colleagues because we found higher facial pain scores at 0, 10 and 20 min postoperation using similar doses of tramadol.
Results from other studies indicate that emergence agitation is closely related to the anaesthetic technique used [14,15]. A total intravenous anaesthesia (TIVA) regimen with propofol used by Özköse and colleagues  provided a rapid and safe emergence from anaesthesia. However, the sevoflurane used may be associated with a higher incidence of postoperative agitation and restlessness . Therefore, we considered that different results noted with tramadol with respect to pain and emergence might be the result of the different anaesthetic methods used.
The haemodynamic responses during surgery were similar in both groups. A decrease and an increase of heart rate and mean arterial pressure after induction and tracheal intubation were found as commonly observed. Although meperidine seemed to be advantageous for its more effective sedative effect, both meperidine and tramadol failed to prevent the changes in heart rate and mean arterial pressure. This may be explained on the basis that such low doses of meperidine and tramadol cannot provide protection from tachycardia and hypertension.
Van den Berg and colleagues reported that meperidine 1.5 mg kg−1 was more effective in reducing reflex responses to nociceptive stimuli during adenotonsillectomy and larger doses of tramadol 6 mg kg−1 might be more appropriate for the same response . The high dose of tramadol 6 mg kg−1 is mandatory for reducing haemodynamic responses; selection of another agent may be more beneficial in that case.
Evaluation of the adequacy of recovery of spontaneous respiration was another objective of our study. Our data demonstrate that tramadol acting on non-opioid receptors has markedly less clinically significant respiratory depression effects than meperidine [17,18]. Even if a slight delay in the return of spontaneous ventilation was found after meperidine, in our view tramadol has no advantage even in the early postrecovery period. On the other hand, tramadol might be favourable in an oral formulation of high potency for pain control in the later postoperative period, i.e. after return to the ward from the recovery room. It should also be remembered that despite the need for adequate treatment of pain postoperation, fear of respiratory depression might result in the withholding of opioids by medical and nursing staff .
In conclusion, we consider that smooth emergence, less agitation and adequate pain relief are more important than a slight delay of the return of spontaneous respiration in the early postoperative period, and meperidine appears to be of greater benefit than tramadol in children undergoing tonsillectomy.
An abstract (A-513) of this work was presented to the Annual Scientific Meeting of the European Academy of Anaesthesiology 2002 (Eur J Anaesthesiol 2002; 19 (Suppl 24): 134).
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