Introduction

The search for an ideal analgesic for use after arthroscopicanterior cruciate ligament (ACL) surgery has become in-creasingly important as greater numbers of operations areperformed. Opioid receptors have long been known in thebrain and central nervous system but have only recentlybeen demonstrated in the periphery. Intra-articular (i.a.)injection of morphine has been found to be effective inproviding analgesia in some [7, 8, 11] but not other stud-ies [6, 13]. It is believed that the analgesic effects of i.a.morphine are optimal in the presence of preexisting inflam-mation, which may partly account for the discrepancy in theresults between the studies [15]. Nonsteroidal anti-inflam-matory drugs (NSAIDs) have been used to good effect inthe treatment of acute musculoskeletal injuries, but littlework has been devoted to evaluating of local NSAIDs inpreventing or reducing postoperative pain [5]. Tenoxicamhas a long half-life of 60–80 h. Local infiltration of the drugconcentrates the pain-control effects in the local area [10].

We planned this study to evaluate the analgesic effectof i.a. injection of tenoxicam and morphine comparedwith a control group on postoperative pain after ACL re-construction.

Materials and methods

The study was approved by our hospital’s ethics committee. In-formed consent was obtained before surgery. In a prospective anddouble-blind study 42 patients of grade I, according to the 1963classification of the American Society of Anaesthesiologists, wererandomized into three groups. Operative procedures included onlyarthroscopic ACL reconstruction using hamstring tendons. Anes-thesia was induced by fentanyl (1 µg/kg) and sodium pentothal(6–7 mg/kg). Vecuronium (0.1 mg/kg) was administered to facili-tate orotracheal intubation. General anesthesia was maintainedwith isofulorane (1–1.5%) and 66% nitrous oxide in oxygen. Ad-ditional fentanyl was not administered during the operation. Ve-curonium (0.03 mg/kg) was additionally administered on require-ment. Monitoring included electrocardiography, noninvasive arte-rial pressure, pulse oximetry, and end-tidal carbon dioxide mea-surements. Residual neuromuscular block at the end of surgerywas antagonized with neostigmine and atropine. At the conclusion

Abstract This study compared theanalgesic effect of intra-articular in-jection of tenoxicam with that ofmorphine on postoperative pain afteranterior cruciate ligament (ACL) re-construction. Forty-two patients un-dergoing arthroscopically ACL re-constructions using hamstring ten-dons underwent the same anestheticprotocol. The patients were random-ized to receive 25 ml normal saline,20 mg tenoxicam in 25 ml normalsaline, or 2 mg morphine in 25 mlnormal saline. Postoperative painwas assessed using a visual analoguescale and measuring analgesic re-quirements. We found both that both

intra-articular tenoxicam and intra-articular morphine provided betteranalgesia than that in the controlgroup. Although pain scores weresimilar between tenoxicam and mor-phine groups 30 min postoperative,the analgesic requirements in withtenoxicam were significantly lowerthan those with morphine group 3–6 h postoperatively.

Keywords Anterior cruciate ligament reconstruction · Morphine ·Tenoxicam

KNEEKnee Surg, Sports Traumatol, Arthrosc(2002) 10 :229–232

DOI 10.1007/s00167-002-0286-y

Gulen GulerSinan KaraogluHediye VelibasogluNesrin RamazanogullariAdem Boyaci

Comparison of analgesic effects of intra-articular tenoxicam and morphine in anterior cruciate ligament reconstruction

Received: 1 July 2001Accepted: 29 January 2002Published online: 27 March 2002© Springer-Verlag 2002

G. Guler · H. Velibasoglu ·N. Ramazanogullari · A. BoyaciDepartment of Anesthesiology, Medical School, Erciyes University, 38039 Kayseri, Turkey

S. Karaoglu (✉ )Department of Orthopedic Surgery and Traumatology, Medical School, Erciyes University, 38039 Kayseri, Turkeye-mail: sinankaraoglu@hotmail.com, Tel.: +90-532-2873135, Fax: +90-352-2255548

of surgery, after all wounds were closed, patients received one ofthree i.a.- injections. Injections in group I (n=12) consisted of 25 ml saline, group II (n=15) 2 mg morphine in 25 ml saline, andgroup III (n=15) 20 mg tenoxicam in 25 ml saline. There was nosignificant difference between the groups with regard to sex, age,height, weight and duration of anesthesia (Table 1). The solutionswere chosen on a randomized basis without informing the surgeonor the assistant who recorded the pain levels. The tourniquet waskept inflated for 10 min after the injection.

Before the operation patients were all instructed in the use ofthe 10-cm visual analogue scale (VAS), with the values 0 and 10 labeled, respectively, “no pain” and “worst pain imaginable.”An observer recorded the VAS 0.5, 1, 2, 3, 4, 5, 6, 12, 24, and 48 h after the operation. All patients were evaluated at rest. Whenthe VAS was found to be 5 or more in patients who complained ofpain in the recovery room, 0.5 mg/kg petidine was administered in-travenously. On return to the ward supplementary analgesia (peti-dine 0.5 mg/kg intramuscularly) was available on request. Detailedrecords were kept of the amount of analgesic drug required. Painscores were analyzed using the Kruskal-Wallis test. When a sig-nificant result was obtained, the Mann-Whitney U test was per-formed to determine between which groups there was a significantdifference; an adjustment was made for multiple comparisons. Theamount of postoperative analgesics and side effects were analyzedusing the χ2 test.

Results

While there was a statistically significant difference inpain scores between the saline group and the other twogroups during the postoperative period, there was no dif-ference between the morphine and tenoxicam groupsthemselves except at 30 min postoperatively (P=0.01; Fig.1).

On the other hand, between 3 h and 6 h postoperativelythere was a statistically significant difference between themorphine and tenoxicam groups in analgesic require-ments (P<0.01, and P<0.0001, respectively; Fig.2). Therewas no significant difference between the groups in sideeffects (Table 2).

Discussion

To minimize of duration of hospitalization and to decreasemedical costs many surgical procedures are being tried onan ambulatory basis. A study evaluating ACL reconstruc-tion reported a cost-savings of up to 58% when this pro-cedure was performed on an outpatient basis [9]. ACL re-construction is associated with a considerable degree ofpostoperative pain. After ACL reconstruction the anatom-ical source of pain may be either the i.a. site of recon-struction, tendon graft donor site, or a combination of thetwo. A study on the localization of pain after ACL surgeryfound that both sites contribute significantly to the pa-tient’s perception of pain [3]. It is known that duration ofhospitalization can be minimized with effective pain man-agement. To perform outpatient surgery safely it is impor-

230

Table 1 General data on the study subjects

Groups Tenoxicam Morphine Control

Sex: M/F 15/0 14/1 12/0Age (years) 26.6±5.7 27.0±6.3 26.2±6.2Height (cm) 171±9 170±11 170±7Weight (kg) 76.5±10.3 76.8±8.9 77.0±10.6Duration of anesthesia 95.6±12.1 98.3±16.9 95.8±11.6(min)

Fig.1 Pain scores of the groups

Fig.2 Analgesic requirements of the groups

tant to avoid the potential adverse systemic reactions ofintravenous narcotics. The use of locally acting analgesicshas increased in popularity because they entail less risk ofsystemic side effects. Some clinical studies have shownthat the use of i.a. opioids is effective in managing post-operative pain after arthroscopic ACL surgery [7, 8, 11].These clinical investigations revealed that i.a. morphinesignificantly reduced pain scores and systemic analgesicuse. Other studies have also failed to show any analgesicbenefit of i.a. morphine after arthroscopic surgery [6, 13].These studies included a variety of arthroscopic surgicalprocedures, and the presence or absence of i.a. inflamma-tion was not addressed. Because there are contradictoryresults on the effectiveness of i.a. morphine and i.a.tenoxicam, which has received only limited attention inthe literature, we decided to compare morphine and tenoxicamgroups with a control group. To standardize the study weadministered the analgesic in 25 ml volume and waited10 min to release the tourniquet after injecting analgesicsolution, as in the study by Joshi et al. [7].

In our study, similarly as in that of Stein et al. [16], theeffect of i.a. morphine appeared at the 3rd h after injectionand decreased the additional analgesic requirements 6 h af-ter injection. Therefore it can be considered that morphinehas maximum analgesic effect at 3–6 h after i.a. injection.

Richardson et al. [15] studied i.a. administration of 1 mg morphine compared to a control group and found nodifference in VAS values at 1 h. However, at 6 and 24 hthey found significantly lower pain scores and analgesicrequirements in morphine group. They also observed that5 mg i.a. morphine matched the effect of intravenous mor-phine (5 mg) without a delay, and this contrasted with thedelayed effect of low-dose morphine (1 mg), suggestingthat this effect may be dose related rather than caused bya delay in the initiation of an inflammatory reaction. Onthe other hand, Reuben et al. [14] concluded that for pa-tients undergoing ambulatory ACL surgery using a multi-modal analgesic regimen the addition of i.a. morphinefailed to provide additional postoperative analgesia. How-ever, they compared morphine with bupivacain and bupiv-acain plus morphine group without a control group.

Although the mechanism of action of NSAIDs is un-known, it is hypothesized that they act via direct modula-tion of peripherally acting pain mediators or via the cen-tral nervous system. NSAIDs could also act locally via in-hibition of prostaglandin synthesis, which is responsiblein part for inflammatory changes following surgical

trauma. Following topical application of proxicam localtissue levels of the drug were significantly greater thanfollowing intravenous administration [12], and a study us-ing topically applied ketoprofen gel found that tissue lev-els of ketoprofen were 100 times higher than plasma [1].Therefore topical application should lead to local prosta-glandin inhibition, thus attenuating sensitization of the pe-ripheral nociceptors and reducing primary hyperalgesia.

Tenoxicam is an NSAID of the oxicam class, with aprolonged elimination half-life [10]. It has been used par-enterally for knee arthroscopy and found to reduce pain inthe 1st h after surgery. As the drug is water-soluble anddoes not require a solubilizing agent, it is particularly suit-able and safe for i.a. injection [2]. El Hakim et al. [4]compared the analgesic effect of i.a. 20 mg tenoxicam andintravenous 20 mg tenoxicam on postoperative pain afterknee arthroscopy. They noted that i.a. 20 mg tenoxicamprovides better analgesia and reduces the requirement ofsupplemental analgesics. Another study comparing i.a. 20 mg tenoxicam in 25 ml normal saline and 40 ml% 0.25 bupivacaine shoved that although pain scores weresimilar in groups, and that analgesic requirements werelower on the 1st day postoperatively in tenoxicam group [2].

In our study pain scores in tenoxicam group werelower than those in control group except 1 h postopera-tively. Because the patients with high pain scores weregiven opioid analgesic in the postoperative care unit after30 min, and the analgesic effect of opioid analgesic lasts 1 h postoperative, and this may explain why there were nodifferences in pain scores 1 h postoperatively. VAS valuesin the tenoxicam group were lower than those in the mor-phine group at all times; however, this difference was notstatistically significant except at 30 min. On the otherhand, the number of patients who required additionalanesthetics after 3 and 6 was significantly lower than themorphine group. Since morphine begins to take effect atthis time, it may be concluded that tenoxicam is more ef-fective during these hours than morphine. No statisticallysignificant difference was observed in systemic side effectsduring opioid or morphine analgesics with the dose used.

Morphine and tenoxicam thus proved effective in treat-ing postoperative pain compared to control group, and al-though the tenoxicam and morphine group pain scoreswere similar, it can be said that the effect of tenoxicam ismore rapid and longer lasting, and that tenoxicam also re-duces the requirement of opioid analgesic to a greater ex-tent than morphine does.

231

Table 2 Side effects in thethree groups Tenoxicam (n=15) Morphine (n=15) Control (n=12)

n % % n % P χ2

Nausea or vomiting 3 20 2 14 3 25 >0.05 0.60Pruritus 0 0 2 14 2 16 >0.05 2.45Urinary retention 1 7 3 20 2 16 >0.05 1.16

232

1.Ballerini R, Casini A, Chinol M, Man-nucci C, Giaccai L, Salvi M (1986)Study on the absorption of ketoprofentopically administered in man: compar-ison between tissue and plasma levels.Int J Clin Pharmacol Res 6:69–72

2.Cook TM, Tuckey JP, Nolan JP (1997)Analgesia after day-case knee arthros-copy: double-blind study of intra-artic-ular tenoxicam, intra-articular bupiv-acaine and placebo. Br J Anaesth 78:163–168

3.Curry CS, Brown DL, Ruterbaries L,Raessler KL (1996) Localization ofpain fallowing arthroscopic anteriorcruciate ligament repair using differen-tial local anesthetic infiltration. AnesthAnalg 82:81–87

4.Elhakim M, Fathy A, Elkott M, SaidMM (1996) Intra-articular tenoxicamrelives post-arthroscopy pain. ActaAnaesthesiol Scand 40:1223–1226

5.Gupta A, Axelsson K, Allvin R,Liszka-Hackzell J, Rawal N, AugustiniBG (1999) Postoperative pain follow-ing knee arthroscopy: the effects of in-tra-articular ketorolac and/or morphine.Reg Anesth Pain Med 24:225–230

6.Heard SO, Edwards WT, Ferrari D,Hanna D, Wong PD, Liland A,Willock MM (1992) Analgesic effectof intraarticular bupivacaine or mor-phine after arthroscopic knee surgery: a randomized, prospective, double-blind study. Anesth Analg 74:822–826

7. Joshi GP, McCarroll SM, Brady OH,Hurson BJ, Walsh G (1993) Intra-artic-ular morphine for pain relief after ante-rior cruciate ligament repair. Br JAnaesth 70:87–88

8. Joshi GP, McCarroll SM, McSwiney M,O’Rourke P, Hurson BJ (1993) Effectsof intraarticular morphine on analgesicrequirements after anterior cruciate lig-ament repair. Reg Anesth 18:254–257

9.Kao JT, Giangarra CE, Singer GS,Martin S (1995) A comparison of out-patient and inpatient anterior cruciateligament reconstruction surgery.Arthroscopy 11:151–156

10.Lin CF, Wong KL, Chan YL, WangJM, Wu KH, Wei TT (1998) Compari-son of local infiltration of tenoxicamand intravenous tenoxicam for postop-erative analgesia in herniorrhaphy.Acta Anaesthesiol Sin 36:23–29

11.Lundin O, Rydgren B, Sward L, Karls-son J (1998) Analgesic effects of intra-articular morphine during and afterknee arthroscopy: a comparison of twomethods. Arthroscopy 14:192–196

12.McNeill SC, Potts RO, Francoeur ML(1992) Local enhanced topical delivery(LETD) of drugs: does it truly exist?Pharm Res 9:1422–1427

13.Raya SN, Dickstein RE, Johnson CA(1992) Comparison of postoperativeanalgesic effects of intraarticular bu-pivacaine and morphine following arthroscopic knee surgery. Anesthesiol-ogy 77:1143–1147

14.Reuben SS, Steinberg RB, Cohen MA,Kilaru PA, Gibson CS (1998) Intraar-ticular morphine in the multimodalanalgesic management of postoperativepain after ambulatory anterior cruciateligament repair. Anesth Analg 86:374–378

15.Richardson MD, Bjorksten AR, HartJA, McCullough K (1997) The efficacyof intra-articular morphine for postop-erative knee arthroscopy analgesia. Arthroscopy 13:584–589

16.Stein C, Comisel K, Haimerl E, Yas-souridis A, Lehrberger K, Herz A, Peter K (1991) Analgesic effect of in-tra-articular morphine after arthroscopicknee surgery. N Engl J Med 325:1123–1126

References