IBUPROFEN IN THE MANAGEMENT OF POSTOPERATIVE PAIN

Br.J. Anaesth. (1986), 58, 171-175 IBUPROFEN IN THE MANAGEMENT OF POSTOPERATIVE PAIN H. OWEN, R. J. GLAVIN AND N. A. SHAW In addition to the control of symptoms associated with arthritis, non-steroidal anti-inflammatory drugs (NSAID) can be administered to relieve acute pain (Kantor, 1982). Although effective in the management of mild to moderate pain (Miller, 1981), there are conflicting reports as to the ability of NSAIDs to control postoperative pain. For example, several studies suggest that analgesia provided by an injectable preparation of acetyl salicylate is similar to that provided by parenteral morphine (Kweekel-De Vries et al., 1974; Cashman et al., 1985; Jones et al., 1985). Other investigators, however, were unable to demonstrate similar results (McAteer and Dundee, 1981). Ibuprofen has been used in the treatment of postoperative pain and is as effective as, or superior to, aspirin, codeine, acetaminophen and codeine, or propoxyphene in this context (Miller, 1981; Dionne et al., 198; Slavic-Svircev et al., 1984). In the earliest (although uncontrolled) study of the effects of ibuprofen on surgical wounds, decreases in both pain and inflammation were found (Choo and Lee, 197). We are unaware of any previous double-blind studies using the regular administration of this agent to provide analgesia after abdominal gynaecological surgery. PATIENTS AND METHODS H. OWEN*, M.B., CH.B., F.F.A.R.C J. (University Department of Anaesthesia); R. J. GLAVIN, M.B., CH.B., F.FJV.R.C.S. (Division of Anaesthesia); Royal Infirmary, Glasgow. N. A. SHAW, The Boots Go. PLC, Nottingham. Present address, for correspondence: Department of Anaesthesia, Flinders Medical Centre, Bedford Park, South Australia, 5042, Australia. SUMMARY The effect of the regular administration of ibuprofen on pain following abdominal surgery A double-blind, parallel-group, multiple dose study was approved by the Hospital Ethical Committee. Written informed consent was ob- was investigated in a double-blind placebocontrolled study. The analgesic action of ibuprofen was measured by a reduction in the amount of morphine self-administered from an On-Demand Analgesic Computer. Pain scores, nausea scores and blood loss were similar in both groups, but patients receiving ibuprofen demanded significantly less morphine in the 24 h after surgery. tained from 71 patients scheduled to undergo lower abdominal gynaecological surgery. Patients with a history of peptic ulceration or gastrointestinal bleeding, asthma, or severe cardiac or respiratory disease were excluded. Patients were randomly allocated to receive suppositories containing ibuprofen 500 mg (n = 29) or placebo (n = 1). The suppositories were administered, initially, 60-90 min before surgery, and then every 8 h for 24 h. All patients received an enema on the day before surgery and particular care was taken to ensure that each suppository was correctly inserted and not extruded. The same anaesthetic technique and surgical incision (Pfannenstiel) were used in all patients. Premedication was with temazepam 0 mg administered at the same time as the first suppository. Anaesthesia was induced with thiopentone 4 6 mg kg" 1 and patients then received morphine 0.2 mg kg" 1 i.v. Tracheal intubation was facilitated with a non-depolarizing myoneural blocking drug and the lungs were ventilated artificially with % oxygen in nitrous oxide and 0.5-1% halothane or 1-1.5% enflurane. At the end of surgery, atropine 1.2 mg was

172 administered and residual neuromuscular blockade antagonized with neostigmine 2.5 mg. Following extubation of the trachea, patients were attached to an On-Demand Analgesic Computer (ODAC, Janssen Scientific Instruments, Beerse, Belgium) programmed to deliver 1-mg increments of morphine in 5 % dextrose 5 ml i.v. The lockout interval was 2 min, giving a maximum permitted hourly dose of 0 mg, but the ODAC was set to warn attending staff when morphine 12 mg had been demanded in 1 h. Analgesia was selfadministered for 24 h and the number of demands satisfied every hour was recorded. All patients were nursed on one ward where the staff are skilled in managing and monitoring patients receiving pain relief by patient-controlled analgesia (PCA). Measurements of pain on a nine-point descriptive rating scale (described in figure 1) and nausea on a four-point scale (described in figure ) were made by patients 6 and 24 h after surgery. Prochlorperazine 12.5 mg was administered to patients who vomited. Blood loss during surgery was measured by swab weighing. An attempt to assess the effect of ibuprofen therapy on haemostasis was made by measuring the area of bruising around the wound days after surgery. Eleven patients did not complete the study, two because of a malfunction of the ODAC, five because of failure to administer a suppository at the correct time, three because surgery or anaesthesia was not standardized and one because of excessive histamine release caused by injection of morphine. BRITISH JOURNAL OF ANAESTHESIA TABLE I. Demographic data. Mean ± SD and range n Age(yr) Weight (kg) Height (cm) Ibuprofen 29 40.25 ±8.0 67.0±1.5 161.7±6.5 Placebo 1 42.7±11.0 64.8±1.1 160.8±8.0 TABLE II. Number of patients undergoing surgery Type of surgery Hysterectomy Ovarian cystectomy Other surgery through Pfennenstiel incision Ibuprofen 22 4 Placebo (fig. 2): patients receiving ibuprofen selfadministered significantly less morphine in the postoperative period. Mean cumulative morphine consumption for patients receiving ibuprofen was 9.1 mg (SD 17.1 mg, range 9-128 mg); for the others 48.2 mg (SD 25.1 mg, range 1-129 mg). 6-h Pain scores 25 Statistical analysis Demographic data were compared using an unpaired Student's t test. Differences in pain, nausea, administration of anti-emetic and morphine consumption were analysed with the Wilcoxon/Mann-Whitney test, and a Chisquared test with Yates' correction was used to compare the incidence of vomiting in the two groups. A P value of less than 0.05 was accepted as being statistically significant. RESULTS Both groups were well matched for age, weight, height and operation (tables I and II). Patients became rapidly adept at managing their own pain relief and few patients experienced more than moderate pain (fig. 1). While the pain scores in the two groups were very similar, mean morphine consumption was different throughout the 24 h No pain Mild pain Moderate Sever* Very severe pain pain pain FIG. 1. Comparison of postoperative pain scores on an ordered categories scale. There arefivedescribed categories of pain and four unlabelled interval categories. Black columns = placebo; cross-hatched columns = ibuprofen.

PAIN RELIEF BY IBUPROFEN 17 6O-1 50-1 I 40- I Placebo Ibuprofsn 0. i 1 20-10- 6 12 18 Time after operation (h) 24 Fig. 2. Cumulative postoperative morphine consumption (mean±sem). The difference is significant (P < 0.05). 'c a 0 10 6-h Nausea scores The incidence of nausea was low in both groups (fig. ) although 79% of patients receiving ibuprofen and 58% receiving placebo vomited. This difference did not quite achieve statistical significance. There was no difference in the amount of anti-emetic administered to the two groups. Intraoperative blood loss and the area of postoperative wound bruising were similar in both groups. 0 20 10 24 -h Nausea scores No nausea Mild nausea Moderate Severe nausea nausea FIG.. Comparison of postoperative nausea scores on a four-point ordered categories scale. Black columns = placebo; cross-hatched columns = ibuprofen. DISCUSSION Patient-controlled analgesia is an effective method of relieving postoperative pain (Graves et al., 198; Rosen, 1984). PCA is an "active" system (Welchew, 198) and many patients will still experience some pain. If "passive" background analgesia is also provided, then any reduction in active PCA demands will be a measure of the efficacy of the background analgesic. We have found that the regular administration of ibuprofen reduced the demand for morphine from an ODAC by 20 %. A similar method for measuring analgesic potency of an NSAID has been reported previously (Jones et al., 1985) but, in contrast to these workers, we have used a short lockout interval and have not limited morphine consumption beyond the physical constraints of the lockout

174 BRITISH JOURNAL OF ANAESTHESIA interval, that is a maximum dose of 0 mg h" 1, and we have not, therefore, relied on nursing staff to give discretionary i.m. injections of analgesic. Ibuprofen was administered rectally because a parenteral formulation is not yet available and oral therapy was thought to be inappropriate in the perioperative period. The suppository formulation of ibuprofen used is widely available in Europe and, in common with other propionic acid derivatives, it is absorbed efficiently, although more slowly than by the oral route (de Boer et al., 1982; Boots Co. PLC, 1985). Therapy was initiated before operation because previous work suggested a slow onset time of analgesia from ibuprofen of around h (Slavic-Svircev et al., 1984) and the preoperative administration of ibuprofen has been shown to suppress postoperative dental pain (Dionne et al., 198). The reduction in morphine requirement in patients receiving ibuprofen was present throughout the 24 h after surgery, suggesting that the subsequent regular therapy provided a stable level of background analgesia. In most studies on analgesics, pain scores are used to differentiate the potency of the agent under scrutiny. Apart from difficulty in the analysis of different pain scores and different drug doses, the ethics of subjecting one group of patients to more pain than another is questionable. Using PCA, all patients can titrate themselves to a "low-pain" endpoint, and only the different analgesic requirements of the groups need be considered further. PCA was originally developed to provide an objective measurement of pain (Sechzer, 1968); however, there is a large inter-individual variation in morphine consumption and conclusions cannot be drawn from measurements from small samples. Mean pain scores were low in both groups, but a few patients in each group appeared to limit their morphine intake because of the nausea or vomiting associated with demanded doses. There was, however, no correlation between pain and nausea scores in either group. An ordered categories scale was used to avoid the difficulties reported when using a visual linear analogue to measure pain after surgery (Grossi, Borghi and Montanari, 1985). Both groups received a similar amount of anti-emetic but, despite administering less morphine, the incidence of vomiting was not reduced in the group receiving ibuprofen. If oral therapy had been used, the high incidence of vomiting might have reduced the amount of drug absorbed. Control of cancer pain by oral narcotic therapy can be significantly improved without an increase in adverse effects by concurrent administration of ibuprofen (Ferrer-Brechner and Ganz, 1984; Weingart, Sorkness and Earhart, 1985). In this study there was a reduction in opioid requirement by patients receiving ibuprofen to achieve pain scores similar to those in the placebo group. If ibuprofen is administered in combination with traditional and ineffective (Leading Article, 1978) pulsed opioid therapy after surgery, it may improve the overall relief of pain. Balanced anaesthesia is an integral part of clinical practice and there may also be a place for balanced analgesia after surgery. In common with other NSAID, ibuprofen has side effects from its inhibition of prostaglandin synthesis (Miller, 1981). We have paid particular attention to any effect that may inhibit blood coagulation, but in the dose used ibuprofen affected neither intraoperative blood loss nor postoperative haemostasis as measured by area of wound bruising adversely. In conclusion, the regular perioperative administration of ibuprofen significantly reduced postoperative opioid requirements. There were no adverse effects apparent with this therapy. ACKNOWLEDGEMENTS We wish to thank the nursing staff of Ward and the anaesthetists and gynaecologists at the Royal Infirmary for their help and co-operation. We are grateful to the Boots Co. PLC for financial assistance and for providing supplies of ibuprofen. REFERENCES de Boer, A. G., Moolenaar, F., de Leede, L. G. J., and Breimer, D. D. (1982). Rectal drug administration: clinical phannacokinetic considerations. Clin. Pharmacokin., 7, 285. Boots Co. PLC (1985). Brufen: Experimental, Technical and Clinical Aspect! of Brufen, p. 6. Nottingham: Boots Co. PLC. Cashman, J. N., Jones, R. M., Foster, J. M., and Adams, A. P. (1985). Comparison of infusions of morphine and lysine acetyl salicylate for the relief of pain after surgery. Br. J. Anaeith., 57, 255. Choo, S. Y., and Lee, Y. K. (197). Anti-inflammatory and analgesic effects of Brufen (ibuprofen) on surgical wounds. A clinical study. Korean Central J. Med., 25, 7. Dionne, R. 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