J Int Med Res (1978) 6,152

A Comparison of N aproxen, Indomethacin and Acetylsalicylic Acid in Pain after Varicose Vein Surgery Ulla Aromaa,· MD, and Kari Asp, MD, Department of Anaesthesia, University of Helsinki, Finland

Oral naproxen in doses of500 mg and 750 mg daily was compared with oral indomethacin, 75 mg daily, in a double-blind, completely randomized study of patients with post-operative pain after out-patient varicose vein surgery. Altogether, 120 patients were studied. In the study 750 mg naproxen proved to be equal in respect of analgesic efficacy to 75 mg indomethacin, and it was clearly superior to 1500 mg acetylsalicylic acid. Naproxen, 500 to 750 mg daily, afforded adequate postoperative analgesia in 98% ofpatients. The side-effects were mild. On the basis of the study, naproxen can be recommended as a pain-relieving drug after minor surgery, particularly when an antiphlogistic effect is also desirable.

to widening the choice of drugs, a study was Introduction Radical varicose vein surgery causes a made of the feasibility of using naproxen considerable soft-tissue trauma. In the (Napro syns' ), a non-steroidal antitreatment of post-operative pain a drug with inflammatory analgesic drug with antipyretic both an analgesic and anti-inflammatory effect activity: 6-methoxy-2-naphthyl-propionic acid. is therefore beneficial. Owing to the routine character of the surgical technique, the trauma Patients and Methods is nearly identical in degree in all patients A total of 120 patients participated in the operated on for varicose veins. Such patients study, which was carried out under doubletherefore provide a homogeneous group for the blind conditions. Patients were assigned study of the acute analgesic effect of oral randomly to one of four treatment groups. The drugs had been packaged in identical analgesics. Indomethacin has been used routinely in our envelopes, three tablets for each day, with the clinic for the treatment of pain subsequent to following daily dosages in different groups: varicose vein surgery (Asp 1974).With a view Naproxen 500 mg (Group N 1, 50 patients), naproxen 750 mg (Group N2, 23 patients), indomethacin 75 mg (Group I, 24 patients), *Requests for reprints should be addressed to: acetylsalicylic acid 1500 mg (Group A, 23 Dr. Ulla Aromaa patients). HYKS!Meilahden Sairaala All patients had been subjected, in the Haartmanink, 4 00290 HELSINKI 29, Finland Second Department of Surgery, Helsinki

U Aromaa and K Asp

153

University Central Hospital, to varicose vein surgery on one extremity, in which the great or small saphenous vein was stripped and local excisions and ligation of perforants were performed (Jarvinen, Aromaa & Asp 1976). Either halothane inhalation anaesthesia or analgesic-dominated balanced anaesthesia was employed (Aromaa 1974). All of the patients were women meeting the following criteria: age over 16 (Table 1), not pregnant, not suffering from gastric or duodenal ulcer. All had given their verbal agreement to participate in the trial. The drugs were taken by the patients for six days post-operatively. A questionnaire was distributed in which the patients made daily entries on the degree of pain (using the scale: no pain, slight pain, severe pain, very severe pain), the adequacy of analgesia (satisfactory or unsatisfactory), and the side-effects experienced by them.

Results Although the importance of taking the drugs had been emphasized, a total of seven patients failed to take the drug up to the end of the trial. Three of them discontinued the drug because of a lack of pain, and four owing to sideeffects. Each of the different groups contains one of the latter four. The patients' subjective assessment of the occurrence of pain on the first six postoperative days is presented in Figure 1 and their subjective assessment of the adequacy of medication against pain in Figure 2.

Post-operative pain was encountered most frequently in the patients who received 500 mg naproxen daily or 1500 mg acetylsalicylic acid daily as an analgesic, i.e. groups Nl and A. Only three patients complained of very severe pain, and they belonged to these groups. No differences were noted in the occurrence of pain between groups N2 and I. In the combined naproxen groups 98% of patients considered the abatement of post-operative pain satisfactory with the drug. Patients rated acetylsalicylic acid at 1500 mg per day as the poorest of the medications tested. The questionnaire was used to gather information on a total of ten different unwanted side-effects. Four patients stopped taking the drug because of side-effects in the form of gastro-intestinal disturbances, while the other side-effects were mild. Side-effects were clearly most frequent in group A. Increasing the naproxen dosage from 500 to 750 mg daily (groups Nl and N2) did not increase the frequency or severity of sideeffects. Figure 3 gives a detailed account of the side-effects recorded in the different groups.

Discussion In the present investigation a follow-up study was made of 120 female patients who had undergone a varicose vein operation on one leg. Since their time in hospital was not more than 24 hours, nearly all of the treatment of post-operative pain took place in their homes. For this reason the pain-relieving medication had to be sufficient in respect of efficacy yet

Table 1 Age distribution of patients

GroupNl Age

Pat.

16-25 26-35 36-45 46-55 56-65 66-75

2 19

Total

11

12 6 50

GroupN2 %

4 38 22 24 12 100

Pat.

2 11

3 6 I

23

Group I %

9 48 13 26 4 100

Pat.

Group A %

Pat.

5 8 5 4

I

4 33 33 9 17 4

24

100

23

I

8 8 2 4

I

Total %

4 22 35 22

Pat.

%

17

6 43 30 25 15

5 36 25 21 12

100

120

100

The Journal of International Medical Research

154

0

50

100%

0

1

,

2

2

3

N1

4

3

5

6

6

1

1

2

2

3

3

N2

5

6

6

1

1

2

2

3

3

4

4

5

5

6

6

1

1

2

2

3

3

A

4

5

6

6

••

Pain-free

A

4

5

0 0

N2

4

5

II Unsatisfactory Effect

Slight pain Severe pain

2? %

N1

4

5

4

10

Fig 2

Very severe pain

Fig 1

Fig 1 Incidence of pain on first to sixth post-operative days in groups N I (naproxen 500 mg daily), N2 (naproxen 750 mg daily), I (indomethacin 75 mg daily) and A (acetylsalicylic acid 1500 mg daily) Fig 2 Patients' subjective assessment of analgesic effect on first to sixth post-operative days in groups Nl , N2.1 and A

U Aromaa and K Asp

%

155

%

NAUSEA

~ 1

40 ]

_2_ ·--3--4---5----6---,~

PERSPIRATION 60-,------------------,

1

2

4

3

5

6

40-i-~------------

':j

20

o

VOMITING 40-.-----------------,

1

2

3

4

5

6

STOMACH TROUBLE 20-,-----------------,

1

2

3

4

5

DIZZINESS 60-r----------------,

1

2

3

4

5

6

FATIGUE

100~----------------.

6 75.,-__- - - - 50

10

25

o

o DIARRHOEA

20

1

2

3

4

DRY MOUTH -----, 80-r-----------------,

5

6

40

10

0-

0

ECZEMA 20.,..----------------,

1 10

2

---- -- -- ----

2

3

4

5

3

4

5

6

-1:Iiiiii~1----~---------~----1 ~~B1

HOT WAVES

6

-

Fig 3/ncidence of unwanted side-effects on first to sixth post-operative days in groups NI, N2, / and A

156

The Journal ofInternational Medical Research

safe, and since the operation involved a fairly large tissue trauma, an antiphlogistic effect in addition to analgesic action was beneficial. Patients with varicose veins constitute a good series for studying the effect of analgesic medication as they are generally physically healthy and no other local inflammatory processes are present. Furthermore, the surgical procedure is largely identical in every patient. In previous studies naproxen was mainly used for the treatment of rheumatic and arthritic diseases (Lussier et al 1973, Hill, Hilary & Hill 1973, Helby-Peterson, Ibfelt & Rossel 1973, Eberl et al 1973), while in a few studies only the effect ofnaproxen on postoperative pain was clarified. Stetson et al (1973) found that after major surgery the pain was too severe to be fully relieved by naproxen. Their results still provide clear-cut evidence of the analgesic efficacy of naproxen. Ruedy and McCullogh (1973) elicited a satisfactory result in 66% of patients in treating pain after orthopaedic surgery, and they achieved an equivalent result in dental surgery. In the present study the comparison between naproxen and acetylsalicylic acid and indomethacin revealed that the effect of naproxen 750 mg daily was as good as that of indomethacin 75 mg daily and that the effect of naproxen 500 mg per day was almost as good. Both naproxen dosages were superior to 1500 mg acetylsalicylic acid daily in efficacy. Erica Szanto (1974) reported that 500 mg naproxen was equivalent in pain relief to 150 mg indomethacin, though the side-effects were less pronounced with naproxen. Side-effects were mild and indeed rarely occurred: in only two cases was it necessary to discontinue naproxen treatment. It should be pointed out here that many of the symptoms recorded as side-effects were probably due to surgery and anaesthesia (Aromaa 1974). Our more frequent side-effects compared with those reported by others may also be due to the fact that our treatment period was comparatively short, for instance compared with those in joint diseases. It has been observed that side-effects distinctly decrease with increasing periods of treatment (Szanto 1974). And it seems obvious that the active and detailed questioning about side-effects has a provocative effect; as a result side-effects of

quite minor intensity and clinical significance have also been recorded. When questioned about the adequacy of relief from pain, 98% of the patients who received naproxen reported satisfaction. On the strength of our study, we can state that naproxen affords sufficient analgesia in the ambulant treatment of varicose vein surgery and that it is a worthwhile alternative owing to its low incidence of side-effects, particularly since, according to Roszkowski et al (1971), the analgesic effect of naproxen only occurs in pain associated with an underlying inflammatory reaction. REFERENCES Aromaa U (1974) Anaesthesia for out-patient varicose vein surgery with special reference-to recovery. Annales Chirurgiae et Gynaecologiae Fenniae 63, Suppl187 AspK (1974) Indomethacin treatment following surgery for varicose veins. A double-blind comparison against placebo. Journal of International Medical Research 2, 203 Eberl R, Tausch G, Sochor H & Binzus G (1973) Ergebnisse eines offenen Versuches mit Naproxen bei Polyarthritis chronic a und anderen Erkrankungen des rheumatischen Formenkreises. Scandinavian Journal of Rheumatology, Suppl 2, 150 Helby-Petersen P, Ibfelt H & Rossel I (1973) A double-blind crossover comparison ofnaproxen and placebo in rheumatoid arthritis. Scandinavian Journal ofRheumatology. Suppl2, 145 HiII,HilarySF&HiIIAGS (1973) Naproxen in ankylosing spondylitis. Scandinavian Journal ofRheumatology, Suppl 2, 121 Jarvinen P, Aromaa U & Asp K (1976) Short-stay varicose vein surgery. Annales Chirurgiae et Gynaecologiae Fenniae 65, 52 Lussier A, Myhal D, Boost G, Varady J, Segre E & Strauss W (1973) Long-term study of naproxen challenged by a short-term double-blind crossover study with placebo in rheumatoid patients. Scandinavian Journal of Rheumatology, Suppl 2, 113 Roszkowski A P, Rooks W H, Tomolonis A J & Miller LM (1971) Anti-inflammatory and analgesic properties of d2-(6=methoxy-Z-naphtyl-propionic) acid (naproxen). Journal of Pharmacology and Experimental Therapeutics 179, 114 Ruedy J (1973) A comparison of the analgesic efficacy of naproxen and acetylsalicylic acid-codeine in patients with pain after dental surgery. Scandinavian Journal of Rheumatology. Suppl 2, 60 Ruedy J & McCullogh W (1973) A comparison of the analgesic efficacy of naproxen and propoxyphene in patients with pain after orthopaedic surgery. Scandinavian Journal of Rheumatology, Suppl 2, 56 Stetson J B, Robinson K, Wardell W M & Lasagna L (1973) Analgesic activity of oral naproxen in patients with post-operative pain. Scandinavian Journal of Rheumatology, Suppl 2, 50 Szanto E (1974) Naproxen - ett nytt antiflogistikum. Ldkartidningen 71, 3789