Nonsteroidal antiinflammatory drugs for postthoracotomy pain A prospective controlled trial after lateral thoracotomy Diclofenac (Voltarol) as an adjunct to papaveretum for pain relief was examined by a prospective, randomized trial in 44 patients who had lateral thoracotomies. Patients given diclofenac, 75 mg intramuscularly twice daily, required less papaveretum in the first 3 days after operation (p < 0.005) and had lower pain scores on a visual analog scale on aU 5 postoperative days (p = 0.02 to <0.001); their respiratory vital capacity on the first postoperative day was also significantly higher (p < 0.02). Diclofenac is a useful adjunct in the management of postthoracotomy pain. (J THORAC CARDIOVASC SURG 1992;103:17-20)
M. Rhodes, MA, FRCS, I. Conacher, MD, FFARCS, G. Morritt, FRCS, and C. Hilton, FRCS, Newcastle Upon Tyne, England
Etoperative pain is traditionally controlled with intramuscular narcotics, but after a thoracotomy this may be associated with difficulties because of the painful nature of the incision. Addition of systemic and intrathecal narcotics improves analgesia at the risk of greater respiratory depression, and intercostal nerve blockade or cryotherapy is less effective than might be expected.' We have examined the value of a nonsteroidal antiinflammatory compound (NSAID) combined with conventional opiate analgesia in this clinical situation. This has been done in a double blind, controlled trial during which measurements were made of postoperative opiate requirements, pain scores, and pulmonary function. Diclofenac sodium (Voltarol) was chosen because it is one of the few NSAIDs available as an intramuscular preparation.
Patients and methods Forty-four consecutive patients with no history of peptic ulceration or adversereactions to NSAIDs wererecruitedduringa period of 3 months. Lateral thoracotomywas performed for a varietyof reasons, most of them related to carcinomaof From the Cardiothoracic Unit, Freeman Hospital, Newcastle Upon Tyne, England. Received for publication May I, 1990. Accepted for publication Oct. 9, 1990. Address for reprints: Mr. M.Rhodes, Department ofSurgery, University ofNewcastle Upon Tyne, Framlington Place, Newcastle Upon Tyne, England. 12/1/26448
Table I. Operations at thoracotomy* No. ofpatients Operativeprocedure
Pneumonectomy Lobectomy Inoperable Pleurectomy Open lung biopsy Celestin insertion Pericardial window Belsey Mark IV Esophagectomy Empyema decortication
4 5 4 3 I I I I
5 6 2 2 I I
o I I
'Operative procedures undertaken atthoracotomy on 20 patients in group I who received papaveretum alone for analgesia and 19 patients in group 2 who were given additional diclofenac, 75 mg every 12 hours for 72 hours after thoracotomy. Patients recorded asinoperable all had carcinoma ofthe lung that was deemed to be resectable preoperatively but found tobe unresectable at thoracotomy. the bronchus (Table I). Informed consent was obtained from each patient beforerandomization into one of two groups by a predetermined numerical sequence. Neither the patient nor the investigator (M. R.) was aware of the patient's group until the sixth postoperative day. The same anesthetictechniquewas used in all patients.Thiopentalwas usedfor induction after a bolusof fentanyl (ISO to 200 !Lg), and vecuronium (7 to 10 mg) was given for muscle relaxation. Bupivicaine (70 to 100 mg) with epinephrine was injected into the paravertebralspacescorresponding to the fifth to eighth intercostal spaceson the side of the operation. At the end of the operationeach patient wasgiven papaveretum.f to 20mg,depending on the patient's age,sex,and weight. On the first postoperative day, in the high-dependency unit, all 17
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PAIN SCORE WORST THINKABLE PAIN
Fig. 1. Visual analog pain scores were recorded with a scale from I to 10, which was explained to the patients at the time of consent. Patients were asked to indicate their postoperativepain by pointing to their positionon the scale on the first 5 postoperative days.
Table III. Respiratory vital capacity*
Table II. Pain scores* Day
\ 2 3 4 5
7.\ 6.6 5.4 4.2 3.6
2.0 2.8 3.1 2.9 3.\
4.5 2.3 1.5
3.2 2.2 2.1 2.0 1.8
<0.\ <0.005 <0.005 <0.005 <0.02
'Daily mean scores of pain assessed by a VAS in 20 patients given papaveretum only (group I) and 19 given additional diclofenac, 75 mg every 12 hours (group 2). Standard deviations (SDs) are also given with p values for each daily comparison calculated with the Mann-Whitney U test and adjusted with Bonferroni's inequality for five repeated tests.
patients were givenan intravenous infusion of papaveretum, at a variable rate determined by their pain. Thereafter, on days 2 to 5, they were given intramuscular papaveretum (5 to 20 mg) as required by their symptoms, and this was not usually more than every 3 hours. Those randomized to receive the NSAID were givendiclofenacsodium, 75 mg intramuscularly every 12 hours, commencingwith their premedicationand continuingfor 72 hours. Patients were unaware of their group. All were given a variable number of injections of papaveretum in addition to routine venipunctures and withdrawal of arterial samples for bloodgas analysis.On the sixth postoperativeday patients were asked whether they had been aware of their treatment group. The amount of papaveretum required in each 24-hour period was recorded. The severityof pain was recorded each day about 6 PM with the aid of a visual analog scale (VAS) (Fig. I). The scale, from 0 to 10,had previously been shownto patients at the time of consent, and its use was explained then. This proved helpful, particularly during the early postoperativeperiod. Pulmonary function tests were performed with a vitalograph, and the vital capacity was measured preoperativelyand on the first and fourth postoperativedays (days 2 and 5). Comparisons of papaveretum consumption, daily pain scores,and vital capacity were made by means of the Mann-Whitney U test for nonparametric data.
Results The study was completed in 39 of the 44 patients. Twenty (11 male), with an average age of 58.1 years (range 26 to 71), were given papaveretum only (group 1). The remaining 19 (12 male), with an average age of 58.3 years (range 37 to 80), were also given diclofenac (group
Preop Oay 2 Day 5
2.80 1.29 1.80
0.79 0.57 0.72
2.81 1.78 1.86
1.06 0.60 0.53
'Preoperative and postoperative respiratory vital capacity in 20 patients given papaveretum only (group I) and 19 given additional diclofenac, 75 mg every 12 hours for the first 72 hours after thoracotomy (group 2). p Values are calculated with use of the Mann-Whitney U test. SO, Standard deviation.
2). The operative procedures undertaken in the two groups were similar (Table I). Five patients were excluded from the final analysis, four in group I and one in group 2. One patient in group I had renal failure (creatinine concentration rising to 720 mg/L) and was withdrawn after 24 hours, one required reventilation on the second postoperative day, and two died (one of myocardial infarction and the other with acute pulmonary edema). In group 2 one patient had transient renal impairment 24 hours after operation, with a serum creatinine concentration of 200 mg/L. The mean consumption of papaveretum during the first 72 hours in patients from group 1 was 75.5 ± 37 mg (standard deviation) compared with 45.6 ± 17.2 mg in group 2 (p < 0.005) (Fig. 2). During the subsequent days, 4 and 5, two patients in group 1 required further opiate but none of those in group 2 needed any. Pain scores (V AS values, Fig. 3) fell progressively from day I to day 5 in both groups. On the day of operation the mean value in group 1 was 7.1 compared with 4.5 in group 2 (p < 0.1). Respective values for day 2 were 6.6 and 2.3 (p < 0.005) and for day 5, 3.6 and 1.8 (p < 0.02). The differences in pain scores between groups I and 2 were significant on 4 of the 5 days after operation (Table 11). The average preoperative vital capacity of the two groups was the same at 2.8 L, which compares with an expected range of 2.54 to 4.44 for our subjects. Approximately the same amount oflung tissue was removed from each group (Table I). On the first postoperative day the
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Fig. 2. Consumption of papaveretum during the first 72 hours after thoracotomy. Twenty patients were given papaveretum only (group I), and 19 were given additional diclofenac, 75 mg every 12 hours (group 2); respective mean valueswere 75.5 mg ± 37 standard deviationand 45.6 mg ± 17.2 standard deviation (p < 0.005; Mann-Whitney U test).
M 30 I
en >- 24 <: .9 en w 18 a:
en en 12 <:
:::t :::J en
• •• ••
Fig. 3. Pain scoresassessed by VAS from 0 to 10 are combined for the first 3 days after operation in 20 patients given papaveretum only (group 1) and in 19 givenadditional diclofenac, 75 mg every 12 hours (group 2); respective mean values were 19.2 ± 5.8 (standard deviation) and 8.3 ± 5.5 (standard deviation) (p < 0.001; Mann-Whitney U test).
mean vital capacities were 1.29 Land 1.78 L for groups I and 2, respectively (p < 0.02). By the fourth postoperative day (day 5), however, the vital capacities of the two groups were similar at 1.8 and 1.86 L (Table III). When patients were asked about awareness of their treatment group, 24 patients were totally unaware. Of the 15 who hazarded a guess, only 8 were correct.
Discussion The major findings of this study were that patients given diclofenac required less opiate analgesia after operation, their pain scores were lower throughout the study period, and respiratory function assessed by their vital capacity was better on the first postoperative day compared with the patients given papaveretum only for anal-
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gesia; all these differences achieved statistical significance. The findings are valid because the study was double blind and included an adequate number of patients who were randomized into the two treatment groups to avoid any bias that might influence the outcome. The statistical differences achieved were considerable. The measurements of preoperative vital capacity were in the low to normal range, which is not surprising in a group of patients who were largely smokers. Many of the patients were undergoing operations for carcinoma of the bronchus. The improved values in group 2 on the first postoperative day are remarkable in view of the increased number of patients undergoing lung resection in that group. Diclofenac sodium is a potent NSAID available for intramuscular administration, and, although initially developed for the relief of musculoskeletal pain.? it now has an established place in the treatment of ureteric colic, where it is more effective and associated with fewer problems than traditional opiate analgesia.' It has been used after both laparotomy" and hip replacement.l where it was found to reduce opiate requirement and provide more effective analgesia in the first 24 hours after operation. After laparotomy the mean arterial carbon dioxide tension of patients given diclofenac was lower than in the control group, indicating improved respiratory function. NSAIDs have also been examined after thoracotomy by three groups. Keenan and coworkers? found that rectal indomethacin provided effective adjuvant analgesia during the first 48 hours after a thoracotomy. Diclofenac was the NSAID studied by the other two groups.?,8 Both found that it gave effective analgesia in the first 48 hours after operation. Casali and Silvestri? compared it with placebo, and Hamdy and coworkers.t in an abstract, reported findings similar to ours. The additional benefits of more adequate analgesia with less opiate usage are that physiotherapy can be more effective at an earlier stage with better expectoration of secretions from the large airways. It is noteworthy that the physiotherapists readily identified those receiving diclofenac because of their improved analgesia and better cooperation in the early phases after operation. The
potential hazards of an NSAID are gastrointestinal bleeding (which was not observed in our patients) and renal impairment; one patient in each group was withdrawn because of impaired renal function. There was no evidence of increased blood loss after operation in patients receiving diclofenac. The results of this study suggest that diclofenac is a useful adjunct for the relief of pain in patients after thoracotomy. The preparation should perhaps be examined more extensively in this clinical situation so that its true value and limitations might be more fully evaluated. We are grateful to members of the pulmonary physiology laboratoryfor help with the pulmonaryfunction testsand to the nurseson wards 25A, 25, and 30 at the Freeman Hospital.Statistical advice was provided by J. Matthews, MA, PhD, medical statistician, University of Newcastle Upon Tyne, England.
6. 7. 8.
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