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Anesth Analg 2000;90:672-676
© 2000 International Anesthesia Research Society

REGIONAL ANESTHESIA AND PAIN MEDICINE

The Analgesic Efficacy of Intravenous Tenoxicam as an Adjunct to Patient-Controlled Analgesia in Total Abdominal Hysterectomy

Fotini Danou, MD, DEAA*, Andia Paraskeva, MD*, Theodoros Vassilakopoulos, MD{dagger}, and Argyro Fassoulaki, MD, PhD, DEAA{dagger}

*Department of Anesthesia, St. Savas Hospital; and {dagger}Department of Critical Care, Evangelismos Hospital, Athens, Greece

Address correspondence and reprint requests to Fotini Danou, MD, DEAA, 25th March St., No. 30, 15561 Athens, Greece. Address e-mail to fotinidanou{at}yahoo.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Nonsteroidal antiinflammatory drugs may reduce postoperative opioid consumption. We evaluated the analgesic efficacy of preoperatively administered tenoxicam in patients undergoing total abdominal hysterectomy. Patients were randomly assigned to receive IV either normal saline 4 mL (Group NS), tenoxicam 20 mg (Group T20), or tenoxicam 40 mg (Group T40) before the induction of anesthesia in a double-blinded fashion. Patient-controlled analgesia with fentanyl was used to assess postoperative opioid requirements. Pain was evaluated by visual analog scale at 2, 4, 6, 8, and 24 h postoperatively. Intraoperative bleeding as assessed by the surgeon, incidence of nausea, and gastrointestinal symptoms were recorded. No statistically significant difference was identified between groups in fentanyl consumption or pain scores. The incidence of nausea was similar in all groups. Two patients in Group T20 and two in Group T40 exhibited mild gastrointestinal symptoms. Intraoperative oozing was noted in two patients in Group T40. We conclude that patients undergoing total abdominal hysterectomy and receiving fentanyl via patient-controlled analgesia postoperatively do not benefit from tenoxicam pretreatment. On the contrary, the drug may be associated with an increased incidence of side effects.

Implications: The preoperative administration of 20 or 40 mg IV tenoxicam does not reduce fentanyl consumption via Patient-Controlled Analgesia, compared with placebo, after total abdominal hysterectomy. Additionally, tenoxicam may increase intraoperative bleeding and gastrointestinal side effects.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
It has been advocated that multimodal analgesia may improve postoperative pain management and reduce opioid-related side effects (1). Accordingly, nonsteroidal antiinflammatory drugs (NSAIDs) have been used as adjuncts to opioid analgesics. Certain studies demonstrate opioid-sparing effects of diclofenac (2), indomethacin (3), and ketorolac (4) after a variety of operations, whereas others conclude that NSAIDs do not offer significant advantages (5,6). The reasons for this discrepancy may be the different pharmacodynamic and pharmacokinetic properties of the NSAIDs (7), doses used (8), and the timing of administration (9).

Tenoxicam is a NSAID with a prolonged analgesic action, because of its long elimination half-life of 60–75 h, and can be administered IV (10). Certain studies have demonstrated the efficacy of 20 mg IV tenoxicam after caesarean delivery (11) and thoracic surgery (12). Others suggest that a dose of 40 mg may be more appropriate in the postoperative setting (8,13). However, no study has compared the efficacy of the two dosage regimens or shown whether increasing the dose is associated with more significant side effects.

We evaluate the analgesic efficacy of 20 and 40 mg of tenoxicam, administered preoperatively, in patients undergoing total abdominal hysterectomy.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After obtaining approval from our institutional ethics committee and patient-informed consent, we studied 45 patients (30–59 yr), ASA I and II, undergoing total abdominal hysterectomy. They were randomly assigned to receive IV either 4 mL normal saline (Group NS), 20 mg of tenoxicam (Group T20), or 40 mg of tenoxicam (Group T40) 10 min before the induction of anesthesia by an independent assistant. Exclusion criteria were obesity, history of peptic ulcer, bleeding disorders, chronic use of NSAIDs, ß-blockers, Ca2+-channel blockers, or sedative drugs (14). Obese patients were defined as those exceeding the ideal body weight by 30%. All patients were briefed on the use of the patient-controlled analgesia (PCA) pump during the preoperative visit and the visual analog scale (VAS).

Premedication was omitted. Monitoring included electrocardiogram, heart rate, noninvasive blood pressure, pulse oximetry, end-tidal carbon dioxide concentration, inspired oxygen concentration, and end-tidal volatile anesthetic concentration. After 3 min of preoxygenation, anesthesia was induced with thiopental 5 mg/kg and fentanyl 5 µg/kg IV. Intubation was facilitated by vecuronium 0.1 mg/kg IV. On peritoneal incision, midazolam 0.05 mg/kg IV was administered and anesthesia was maintained with an end-tidal isoflurane concentration of 0.5%–1.5%. Muscle relaxation was sustained with incremental doses of vecuronium 0.03 mg/kg guided by monitoring of neuromuscular junction. At the end of the operation, residual muscle relaxation was reversed with atropine 1.2 mg and neostigmine 2.5 mg IV.

In the postanesthesia care unit, pain was treated with fentanyl in increments of 50 µg IV as required by the patient, by an independent anesthesiologist, who was blinded to the patient’s group assignment. The total dose administered was recorded. At that point, the PCA device (Lifecare 4200, Abbott, Abbott Park, IL) with a 30-mL syringe containing fentanyl 50 µg/mL, was connected to a peripheral vein. It was set to deliver a bolus dose of 50 µg with a lockout interval of 60 min for a period of 8 h postoperatively. Patients had been informed that a rescue dose of analgesic medication (50 µg of IV fentanyl) would be available to them as needed. Intramuscular (IM) dimenydrinate was used to treat nausea and vomiting. Pain scores were assessed at 2, 4, 6, 8, and 24 h postoperatively at rest and during coughing, by using a VAS scale (0–10 cm). The investigator conducting the VAS assessment was blinded to the patient’s group assignment. Fentanyl consumption, including rescue doses, was recorded, as was incidence of nausea and gastrointestinal symptoms. The dose of fentanyl reported 2 h postoperatively includes both fentanyl administered in the postanesthesia care unit as increments, as well as that self-administered. Intraoperative bleeding diathesis was assessed by the surgeon, who was blinded to the patient’s group, and was recorded as "increased oozing and difficulty to control it." Eight hours postoperatively, PCA was discontinued, and pain was treated with pethidine 1 mg/kg IM as required.

A power analysis indicated that to obtain a 90% power of detecting a clinically relevant difference of 100 µg total fentanyl consumption, 15 patients were required in each group. The normality of the distribution was tested by using the Kolmogorov-Smirnov two-sample test. Demographic data, pain scores, and fentanyl consumption at each time point were statistically evaluated by using one-way analysis of variance, with the least significant difference test, post hoc. The incidence of side effects was compared with the two-tailed Fisher’s exact test. P < 0.05 was considered statistically significant.


   Results
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 Abstract
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Discussion
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The patients did not differ in age (45 ± 3, 47 ± 4, 46 ± 6 yr), body weight (65 ± 8, 71 ± 9, 66 ± 7 kg), or height (161 ± 5, 162 ± 7, 164 ± 5 cm) in the NS, T20, and T40 groups, respectively. Duration of surgery (time from skin incision to skin closure) was not significantly different between Groups NS and T40 (93 ± 25 and 109 ± 27 min, respectively), but was slightly longer in Group T20 (118 ± 34 min) (P < 0.05 between Groups NS and T20). Two patients in Group NS and three patients in Group T20 required rescue doses of fentanyl. No patient exhibited excessive sedation requiring alteration of the PCA settings or discontinuation. The VAS scores at rest and during coughing are presented in Figs. 1 and 2. No statistically significant difference among groups was observed. A difference between Groups NS and T40 was noted 4 h postoperatively in the VAS scores both at rest (5.0 ± 2.0 vs 3.5 ± 2.0, respectively) and during coughing (7.0 ± 2.0 vs 5.0 ± 2.0), but still failed to reach statistical significance. Accordingly, fentanyl consumption was similar in the three groups at all time intervals (Table 1). The largest dose was required between 0 and 2 h postoperatively in all groups, and the lowest between 4 and 6 h postoperatively. During the latter period, patients in Group T40 used less fentanyl (57 ± 37 µg) than those in Group NS (90 ± 21 µg) and in Group T20 (73 ± 26 µg), but these differences did not reach statistical significance. All patients required only one dose of pethidine IM during the first postoperative night, except for one patient in Group NS, who required two doses.



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  		Figure 1. Visual analog scale scores in each group at rest 2, 4, 6, 8, and 24 h postoperatively. Values are mean ± SD. NS, T20, and T40 stand for the groups that received normal saline, tenoxicam 20 mg, and tenoxicam 40 mg, respectively.

 

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  		Table 1. Fentanyl Consumption (Mean ± SD) in µg in Each Group of Patients 2, 4, 6, and 8 h Postoperatively and the Total Consumption Over 8 h Postoperatively
 


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  		Figure 2. Visual analog scale scores in each group during cough 2, 4, 6, 8, and 24 h postoperatively. Values are mean ± SD. NS, T20, and T40 stand for the groups that received normal saline, tenoxicam 20 mg, and tenoxicam 40 mg, respectively.

 
The overall incidence of nausea was 58% and did not differ among the groups (7, 9, and 10 patients had nausea in Groups NS, T20, and T40, respectively). Thirteen percent of the patients who received tenoxicam (two patients in Group T20 and two in Group T40) complained of epigastric pain, as opposed to none in the control group, but no severe gastrointestinal symptoms were recorded. Two patients who received 40 mg of tenoxicam exhibited intraoperative oozing, compared with none of the patients who received either saline or 20 mg of tenoxicam.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Our results demonstrate that IV tenoxicam administered before the induction of anesthesia does not have a sparing effect on postoperative PCA fentanyl consumption.

Tenoxicam is the only NSAID licensed for IV use in certain countries, including Greece. Furthermore, because of its pharmacokinetic profile (10), it can be administered once daily, which renders it attractive for postoperative analgesia.

Previous studies in patients undergoing various operations have shown that tenoxicam is associated with an opioid-sparing effect (11,12,15,16). Nevertheless, when Vandermeulen et al. (9) compared the efficacy of tenoxicam in a variety of abdominal and orthopedic operations, they found a significant reduction in morphine use only after abdominal hysterectomy. We therefore deduced that this surgical population would be suitable to study the dose-response characteristics of tenoxicam.

We administered tenoxicam before the induction of anesthesia because Colbert et al. (17) supported the preemptive efficacy of tenoxicam, and Vandermeulen et al. (9) suggested that the lack of opioid-sparing effect after certain operations may have been a result of its postoperative use.

We decided to apply a longer lockout interval in the PCA settings than those we normally use in routine practice in our department. These PCA settings are also longer than those reported by other investigators (2,18) and probably not sufficient to ensure good postoperative analgesia. However, obtaining complete analgesia might have masked a possible favorable effect produced by tenoxicam (19). By encouraging patients preoperatively to request rescue doses of analgesic when needed, any beneficial effect of tenoxicam among the groups could be identified. In fact, two patients in the NS group and three patients in the T20 group required rescue doses of fentanyl, which did not alter the overall fentanyl consumption between the groups, thus indicating adequate pain relief.

In accordance with our findings, Windsor et al. (13) have shown that tenoxicam does not reduce analgesic consumption after day-case laparoscopy. Other investigators reached similar conclusions using diclofenac in general abdominal surgery (20) and cholecystectomy (5).

In our study, 40 mg of tenoxicam tended to reduce VAS scores, particularly 4 h postoperatively, and fentanyl consumption between 4 and 6 h, but no significance was obtained. A possible explanation may be the large variability of both pain scores and opioid use, which has been previously noted (9). Group T20 tended to use larger doses of fentanyl. This may be a result of the longer duration of operation in these patients.

Based on the analysis of power, our negative results cannot be attributed to the sample size. The poor analgesic effect of tenoxicam in abdominal hysterectomy may be explained by certain pharmacokinetic characteristics, such as low lipid solubility and high protein binding, which prevented a central effect (10).

The incidence of nausea was similar in all groups. This is in accordance with most studies, including those that show an opioid-sparing result after NSAID use (6,9,12,15). Gastrointestinal symptoms were minor in both Groups T20 and T40. In two patients who received 40 mg of tenoxicam, significant intraoperative oozing was reported by the surgeon. Similar findings were obtained by Rogers et al. (21), who have demonstrated increased blood loss when ketorolac was administered before as opposed to after surgery. However, none of the patients we studied required blood transfusion or reoperation to control bleeding.

In conclusion, the addition of tenoxicam to PCA with fentanyl offers no advantages in either pain relief or opioid consumption after total abdominal hysterectomy. In contrast, it augments cost and may contribute to an increased incidence of side effects. Thus, based on this study, we do not recommend the use of tenoxicam in total abdominal hysterectomy.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Code W. NSAIDs and balanced analgesia. Can J Anaesth 1993;40:401–5.
  2. Laitinen J, Nuutinen L. Intravenous diclofenac coupled with PCA fentanyl for pain relief after total hip replacement. Anesthesiology 1992;76:194–8.[Web of Science][Medline]
  3. Pavy T, Medley C, Murphy F. Effect of indomethacin on pain relief after thoracotomy. Br J Anaesth 1990;65:624–7.[Abstract/Free Full Text]
  4. Picard P, Bazin J, Conio N, et al. Ketorolac potentiates morphine in postoperative patient-control analgesia. Pain 1997;73:401–6.[Web of Science][Medline]
  5. Colquhoun AD, Fell D. Failure of rectal diclofenac to augment opioid analgesia after cholecystectomy. Anaesthesia 1989;44:57–60.[Web of Science][Medline]
  6. Parker RK, Holtman B, Smith I, et al. Use of ketorolac after lower abdominal surgery. Effect on analgesic requirement and surgical outcome. Anesthesiology 1994;80:6–12.[Web of Science][Medline]
  7. Mather LE. Do the pharmacodynamics of the non-steroidal anti-inflammatory drugs suggest a role in the management of postoperative pain? Drugs 1992;44:1–12.
  8. Roelofse JA, van der Bijl P, Joubert JJ. An open comparative study of the analgesic effects of tenoxicam and diclofenac sodium after third molar surgery. Anesth Pain Control Dent 1993;2:217–22.[Medline]
  9. Vandermeulen EP, Van Aken H, Scholtes JL, et al. Intravenous administration of tenoxicam 40 mg for post-operative analgesia: a double-blind, placebo-controlled multicenter study. Anaesth 1997;14:250–7.
  10. Todd PA, Clissold SP. Tenoxicam: an update of its pharmacology and therapeutic efficacy in rheumatic diseases. Drugs 1991;41:625–46.[Web of Science][Medline]
  11. Elhakim M, Nafie M. I.V. tenoxicam for analgesia during Caesarean section. Br J Anaesth 1995;74:643–6.[Abstract/Free Full Text]
  12. Merry AF, Wardall GJ, Cameron RJ, et al. Prospective, controlled, double-blind study of i.v. tenoxicam for analgesia after thoracotomy. Br J Anaesth 1992;69:92–4.[Abstract/Free Full Text]
  13. Windsor A, McDonald P, Mumtaz T, Millar JM. The analgesic efficacy of tenoxicam versus placebo in day case laparoscopy: a randomized parallel double-blind trial. Anaesthesia 1996;51:1066–9.[Web of Science][Medline]
  14. Cashman JN. The mechanism of action of NSAIDs in analgesia. Drugs 1996;52:13–23.
  15. Liaw WJ, Day YJ, Wang JJ, Ho ST. Intravenous tenoxicam reduces dose and side effects of PCA morphine in patients after thoracic endoscopic sympathectomy. Acta Anaesthesiol Sin 1995;33:73–7.[Medline]
  16. Munro FJ, Young SJ, Broome IJ, et al. Intravenous tenoxicam for analgesia following laparoscopic cholecystectomy. Intensive Care 1998;26:56–60.
  17. Colbert ST, O’Hanlon DM, McDonnell C, et al. Analgesia in day case breast biopsy—the value of pre-emptive tenoxicam. Can J Anaesth 1998;45:217–22.[Web of Science][Medline]
  18. Camu F, Van Aken H, Bovill JG. Postoperative analgesic effects of three demand-dose sizes of fentanyl administered by patient-controlled analgesia. Anesth Analg 1998;87:890–5.[Abstract/Free Full Text]
  19. Morgensen T, Vegger P, Jonsson T, et al. Systemic piroxicam as an adjunct to combined epidural bupivacaine and morphine for postoperative pain relief—a double-blind study. Anesth Analg 1992;74:366–70.[Abstract/Free Full Text]
  20. Tigerstedt I, Janhunen L, Tammisto T. Efficacy of diclofenac in a single prophylactic dose in postoperative pain. Ann Clin Res 1997;19:18–22.
  21. Rogers JEG, Fleming BG, Macintosh KC, et al. Effect of timing of ketorolac administration on patient-controlled opioid use. Br J Anaesth 1995;75:15–8.[Abstract/Free Full Text]
Accepted for publication November 15, 1999.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press