1Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland. 2Department of Otorhinolaryngology, Kuopio University Hospital, Kuopio, Finland. 3Department of Pharmacy, Kuopio University Hospital, Kuopio, Finland*Corresponding author: Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland
Accepted for publication: July 10, 2000
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Abstract |
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Br J Anaesth 2000; 85: 83640
Keywords: analgesia, paediatric; pain, postoperative; analgesics non-opioid, ketoprofen; surgery, otolaryngological
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Introduction |
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More than 50% of children undergoing day-case surgery experience clinically significant pain after discharge.2 3 Furthermore, the pain experienced by the child in hospital after adenoidectomy predicts the behavioural problems and pain at home.4 5 Non-opioid analgesics are effective in the treatment of mild and moderate pain in children.6 Non-steroidal anti-inflammatory drugs (NSAIDs) not only produce good analgesia but also reduce the consumption of opioids and the incidence of adverse events, such as nausea and vomiting.7 Ketoprofen is a derivative of propionic acid and is a commonly used NSAID in adults in many countries. The efficacy and safety of i.v. ketoprofen is also recognized in paediatric patients.4 7
During the perioperative period, oral analgesics may not be absorbed reliably, and therefore i.v. injection and rectal suppositories are used commonly. These routes of administration routes have not been compared adequately.8 Therefore, the aim of this study was to evaluate whether rectal ketoprofen is as effective an analgesic as i.v. ketoprofen for pain management in children after day-case adenoidectomy.
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Patients and methods |
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A randomized, prospective, double-blind, double-dummy, placebo-controlled, parallel-group study design was used. Children were allocated randomly to either of the two ketoprofen groups or to a placebo group. The allocation was computer-generated and a sealed envelope method was used to ensure blinding. Forty-two children received ketoprofen rectally (suppository group), 42 children received ketoprofen i.v. (i.v. group), and 39 children received only placebo (placebo group).
In the suppository group, the children were given ketoprofen rectally 25 mg as a suppository (Ketorin® 25 mg supp., Orion, Espoo, Finland) after induction of anaesthesia but before surgery and placebo i.v. (0.9% normal saline 10 ml). In the i.v. group, the children were given a placebo suppository and ketoprofen 25 mg in 10 ml 0.9% normal saline i.v. injected over 5 min (Ketorin® 50 mg/ml injection, Orion). In the placebo group, the children were given a placebo suppository and an i.v. injection of normal saline. The buttocks were taped together after the insertion of the suppository to avoid displacement. After the operation we checked that the suppository had remained in the rectum. The injections were prepared by a nurse not taking part in the study, and the appearances of the ketoprofen and placebo suppositories were similar, thus ensuring blinding.
A standard anaesthetic technique was used. Each child was premedicated with diazepam 0.5 mg kg1 orally up to a maximum of 10 mg 30 min before induction. EMLA® cream (Astra, Södertälje, Sweden) was used at the venous puncture site. Atropine 0.01 mg kg1 was given i.v. and anaesthesia was induced with thiopental 5 mg kg1 and fentanyl 1 µg kg1 i.v. To facilitate tracheal intubation, cis-atracurium 0.1 mg kg1 was given. Anaesthesia was maintained with 23% sevoflurane (inspired concentration) in 65% nitrous oxide in oxygen with intermittent positive-pressure ventilation. On completion of the procedure, muscle relaxation was reversed with neostigmine 50 µg kg1 and glycopyrrolate 10 µg kg1. All children received fentanyl 1 µg kg1 at induction, and no more opioids were allowed during surgery. For intraoperative fluid maintenance, all children were given 0.9% saline 510 ml kg1 h1.
The adenoids were removed using a curettage technique under visual control. Haemostasis was by temporary nasopharyngeal packs and electrocautery. The operation time was recorded and, at the end of procedure, the surgeon estimated the amount of bleeding using a 5-point scale (0=no bleeding, 5=profuse bleeding).4
After surgery, the children were transferred to the postanaesthesia care unit (PACU), where vital signs were monitored and pain was assessed by specially trained nurses. Postoperative pain was assessed using the Maunuksela scale9 as modified by Nikanne and colleagues (0=no pain, 10=worst pain).4 Pain experienced by the child at rest and during swallowing was assessed continuously and recorded every hour up to 3 h. If the child was in pain with a pain score at rest 3, fentanyl 0.5 µg kg1 i.v. was given. The dose was repeated at 5 min intervals until the pain had diminished to a rating of slight. No more than four doses were allowed in any period of 1 h. No other analgesic medication was permitted during the study. The last pain assessment and recording was made just before discharge. At the same time, the worst pain during the patients stay in the PACU was noted. At discharge, sedation was assessed using a 100 mm visual analogue scale (VAS, left end=full alert, right end=not arousable). All adverse effects were recorded for each patient.
Patients were discharged when they were awake, were able to walk unaided, had had stable vital signs for at least 1 h, had no pain or only mild pain, had not vomited for 1 h, were able to tolerate clear fluid, and had no bleeding. All children received ketoprofen 1 mg kg1 i.v. just before discharge. The discharge was defined as delayed if it was later than 5 h after surgery.
The sample size was based on detecting a difference of 35% or more in the need for rescue analgesic between the i.v. and suppository groups at a significance level of 0.05 with 80% power. Continuous variables were analysed with the KruskalWallis test, and for post hoc analysis the MannWhitney test with Bonferonni correction was used. For the categorical variables, the 2 test was used. P<0.05 was considered statistically significant. Results are presented as number of cases (%), median (10th and 90th percentiles), mean (SD) or mean difference [95% confidence interval (CI)] as appropriate.
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Results |
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For the 88 children who needed rescue analgesics in the PACU, ketoprofen significantly reduced the number of doses of rescue analgesia compared with the placebo group (P=0.038, KruskalWallis test). There was no difference between the two ketoprofen groups.
Of the children who needed rescue analgesics in the PACU, seven out of 28 (25%) in the i.v. group needed three or more doses of rescue analgesics compared with nine out of 27 (33%) in the suppository group; the difference was not significant. In the placebo group, significantly more children [17 out of 33 (52%)] needed three or more doses of rescue analgesia compared with children receiving ketoprofen (i.v./suppository groups vs placebo group: difference 22%, 95% CI 245%, P=0.015, 2 test).
Although the median time to the first fentanyl dose was 23 min (10th and 90th percentiles, 5 and 105 min) in the placebo group compared with 35 (10 and 100) min in the suppository group and 32 (590) min in the i.v. group, the differences were not significant.
There was no significant difference between the study groups in their Maunuksela pain scores during the PACU stay or at discharge. Sedation at discharge was also similar (Table 2). There were no differences between the study groups in the amount of intraoperative bleeding evaluated by the surgeon (Table 3). No children experienced postoperative bleeding that required further surgery, delay in discharge, admission to hospital or any other intervention. There were no differences between the study groups in the incidence of adverse events (Table 4). The most common adverse events were nausea, retching and vomiting [16 out of 123 children (13%)]. Anorectal adverse events did not occur.
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Discussion |
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A study in adults showed that 7393% of ketoprofen is absorbed after administration of a rectal suppository.10 However, drug absorption after rectal administration in children may be delayed and erratic, as shown with paracetamol.11 We believe that one reason for unpredictable absorption could be evacuation of the suppository from the rectum as a result of the defaecation reflex caused by insertion of the suppository. In this study, the problem was avoided by taping the buttocks together after insertion of the suppository. When checked after surgery, none of the suppositories had come out.
Guidelines of the Royal Colleges of Surgeons of England suggest that day cases managed in a dedicated unit should have an inpatient admission rate of no higher than 2 or 3%. In this study, only one child was admitted and discharge was delayed in only eight children. One child had difficulty in passing urine, five children had protracted nausea and vomiting and two children in the placebo group had severe pain. Chung and Mezei evaluated factors predicting a prolonged stay after day-case surgery and found that excessive pain and protracted nausea and vomiting are the most significant factors.12 The overall rate of delayed discharge of 6% in this study was much higher than we have observed in our previous studies.4 7 Normally, day cases recover within a dedicated day-case recovery area but, because of maintenance work, children in this study recovered in the main inpatient recovery ward. We believe that this may explain our high rate of delayed discharge.
Volatile anaesthetics, for example sevoflurane, are common agents for the maintenance of anaesthesia. Sevoflurane allows easy control of the depth of anaesthesia and rapid recovery characteristics, but has been associated with recovery agitation.13 There is increasing evidence that sevoflurane must be combined with an analgesic. Katoh and colleagues showed recently that the use of fentanyl significantly reduced the requirement of sevoflurane.14 Moreover, Davis and colleagues showed that intraoperatively administered NSAID reduced agitation on emergence from anaesthesia.15 The effect of ketoprofen on the need for sevoflurane has not been determined. Since ketoprofen also has a central analgesic effect, it would be interesting to evaluate the interaction between sevoflurane and ketoprofen.16
Rectal administration is used in some countries but, in most cases, the principal reason for choosing the rectal route is based on tradition. In Finland, awake children dislike suppositories.17 Our results show that, during anaesthesia, rectally administrated ketoprofen is an effective alternative to i.v. administration.
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References |
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