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AMBULATORY ANESTHESIA

Postoperative Analgesia at Home After Ambulatory Hand Surgery: A Controlled Comparison of Tramadol, Metamizol, and Paracetamol

Narinder Rawal, MD, PhD^*, Renée Allvin, CRNA, BSc^*, Anders Amilon, MD, Torbjörn Ohlsson, CRN, M Soc Sci, and Jan Hallén, MD^*

Departments of *Anesthesiology and Intensive Care and Hand Surgery, Örebro Medical Center Hospital, Örebro, Sweden

Address correspondence and reprint requests to Narinder Rawal, MD, PhD, Department of Anesthesiology and Intensive Care, Örebro Medical Center Hospital, SE-701 85 Örebro, Sweden. Address e-mail to n.rawal{at}orebroll.se

	Abstract

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We compared in a prospective, randomized, double-blinded study the analgesic efficacy of three drugs in 120 ASA I and II patients scheduled to undergo ambulatory hand surgery with IV regional anesthesia. At discharge, oral analgesic tablets were prescribed as follows: tramadol 100 mg every 6 h, metamizol 1 g every 6 h, and paracetamol (acetaminophen) 1 g every 6 h. Rescue medication consisted of oral dextropropoxyphene 100 mg on demand. Analgesic efficacy was evaluated by self-assessment of pain intensity by visual analog score at six different time intervals during the 48-h study period. Patients also recorded global pain relief on a 5-grade scale, total number of study and rescue analgesic tablets, frequency and severity of adverse effects, sleep pattern, and overall satisfaction. None of the study drugs alone provided effective analgesia in all patients. The percentage of patients who required supplementary analgesics was 23% with tramadol, 31% with metamizol, and 42% with acetaminophen. Tramadol was the most effective analgesic, as evidenced by low pain scores, least rescue medication, and fewest number of patients with sleep disturbance. However, the incidence of side effects was also increased with tramadol. Seven patients (17.5%) withdrew from the study because of the severity of nausea and dizziness associated with the use of tramadol. Metamizol and acetaminophen provided good analgesia in about 70% and 60% of patients, respectively, with a decreased incidence of side effects. Despite receiving oral analgesic medication, up to 40% of patients undergoing hand surgery experienced inadequate analgesia in this controlled trial. Although tramadol was more effective, its use was associated with the highest frequency and intensity of adverse effects and the most patient dissatisfaction. Metamizol and acetaminophen provided good analgesia with a small incidence of side effects. For patients undergoing ambulatory hand surgery, postoperative pain can last longer than 2–3 days, and there is a need for both better education before the procedure and oral analgesic therapy at home.

Implications: Despite pain medication, up to 40% of patients experienced pain at home after ambulatory hand surgery. Of the three analgesic drugs evaluated in this double-blinded study, tramadol was the most effective but was also associated with most patient dissatisfaction because of an increased incidence of nausea and dizziness. Metamizol provided somewhat better analgesia than acetaminophen. There is a need for better oral pain medication at home.

	Introduction

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Hand surgery procedures are often performed on an ambulatory basis, and postoperative pain is a common complaint (1,2). It is usually treated with oral medication, including acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), opioid-containing oral analgesics (e.g., codeine-acetaminophen), or a combination of these. However, many patients still do not achieve effective analgesia at home with these drugs (1,2). Furthermore, in some patients, the role of NSAIDs may be limited by adverse gastrointestinal, hemostatic, and renal effects. Acetaminophen is one of the most widely used analgesics and is generally recognized as a safe and effective drug with a favorable adverse effect profile (3). In recent years, analgesics such as metamizol and tramadol have also become available in Sweden. These analgesics are considered to be more potent than acetaminophen. Metamizol is a nonopioid analgesic with antipyretic, antispasmodic, and antiinflammatory components (4). Tramadol is a synthetic µ-opioid agonist with additional monoaminergic activity (5,6). Tramadol’s analgesic effect has been equated with that of meperidine, but with a more favorable side effect profile. It is not classified as a controlled substance and is believed by some to be of particular value for outpatients undergoing ambulatory surgery (7).

The aim of this prospective, randomized, double-blinded study was to compare the effectiveness of acetaminophen, metamizol, and tramadol in the treatment of postoperative pain in patients undergoing ambulatory hand surgery.

	Methods

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With the approval of the hospital ethics committee and after patient consent, 120 patients who had undergone hand surgery were allocated randomly to one of three groups of equal size. All surgeries were performed between 8:00 AM and 2:00 PM. All patients who were ASA grade I or II and <70 yr old were eligible. Exclusion criteria were alcoholism; drug dependence; psychiatric disease; pregnancy; lactation; and severe allergic, hepatic, renal, cardiovascular, or pulmonary disease. A random number table was used to generate a randomized schedule specifying the group to which each patient would be assigned upon entry into the trial.

All patients received midazolam 2.5 mg IV before surgery. All operations were performed under IV regional anesthesia with 3 mg/kg 1% lidocaine. After surgery, the patients were transferred to the postanesthesia care unit. Postoperative pain in the postanesthesia care unit was treated with the study drug. In case of inadequate pain relief, rescue analgesia was provided by titrated doses of morphine, 1–2 mg IV, until the visual analog score (VAS) was 3 (on a 10-grade scale) in accordance with our hospital policy. Study drugs were packaged identically by a nurse unaware of the contents. Before discharge, the patients were given oral and written information about the study protocol and a patient diary. They also received their analgesic tablets, consisting of the study drug and rescue medication, for 2 days. The analgesic drugs were prescribed as follows: Group P received acetaminophen 1 g every 6 h, Group M received metamizol 1 g every 6 h, and Group T received tramadol 100 mg orally every 6 h. If the study drug was ineffective (VAS > 3), a second dose could be taken after 1 h. If the second dose of study medicine was inadequate, the patients were instructed to take rescue medication, which was a 100-mg tablet of dextropropoxyphene (Dexofen®; Astra, Sodertalje, Sweden).

The patient diary was given to each patient to record analgesic efficacy at home. The diary included separate pages for self-assessment of pain intensity at six different time intervals—three times the day of surgery and three times on the first postoperative day (Fig. 1). Patients were instructed to indicate their pain intensity by a cross on a 10-cm vertical line with the words "no pain" at the bottom end and "worst possible pain" at the top end. Patients were also instructed to complete the diary by answering the following questions for both study and rescue medication: total number of tablets, quality of analgesia on a 5-grade scale, sleep pattern, frequency and severity of adverse effects, satisfaction on a 4-grade scale, and suggestions for improvement. Patients were instructed to provide this information for 2 days—the day of surgery and the day after. A follow-up call was made by a nurse who was blinded to the patients’ medication grouping. At this time, the nurse also reminded the patient to return the completed patient diary in the self-addressed envelope that had been provided at the time of discharge. The patients were instructed to return the questionnaire as soon as they were pain free. Nonresponders were not contacted.

View larger version (28K): [in this window] [in a new window]   Figure 1. Self-assessment of pain at home.

	Results

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Demographic data concerning the patient’s age, sex, duration of surgery, and requirement of morphine were similar in all the study groups ( Table 1). None of the patients was discharged unless the VAS score was <3. There was no difference between the groups regarding VAS scores at discharge. Ten patients did not return the questionnaire. Five belonged to the Tramadol Group, three to the Metamizol Group, and two to the Acetaminophen Group.

The consumption of study tablets at home is summarized in Table 2. On the day of surgery, patients in the Tramadol Group took the largest number of tablets (mean 5.5 ± 1.1 tablets), whereas on Day 2 it was patients in the metamizol group (6.0 ± 2.9 tablets). In the Tramadol Group, the consumption of analgesic medication at home was significantly larger on both postoperative days as compared with the consumption in the Acetaminophen Group (P < 0.001) and only on Day 1 versus the Metamizol Group (P < 0.05). However, on Day 2, patients in the Metamizol Group consumed the largest number of study analgesic tablets (P < 0.05 versus acetaminophen). Patients in the Acetaminophen Group did not follow instructions of 1 tablet every 6 h; it is unclear why they took the tablets every 8–12 h. This may have affected our results. Pain scores were generally small (<3) in all groups, but these were not caused by study drugs alone. About 20%–40% of patients required rescue dextropropoxyphene tablets to achieve good analgesia (Table 2). Tramadol provided the best analgesia, as seen by the small pain scores and requirement of the least rescue medication. The pain scores reached statistical significance only at discharge from the hospital (Fig. 1). Over 30% of patients in the Tramadol Group considered the drug as "too strong," possibly because of the frequent incidence of sedation, dizziness, and other side effects.

The most common side effects were tiredness and nausea, with nausea significantly more common in the Tramadol Group (Table 2). About 40%–60% of patients complained of tiredness: again, the most frequent incidence was associated with the Tramadol Group and the least with the Acetaminophen Group (not significant). Seven patients, all in the Tramadol Group, withdrew from the study because of the severe nausea and vomiting. On the day of surgery, sleep disturbance was more common in the Acetaminophen Group (32%) as compared with the Metamizol Group (21%) and Tramadol Group (18%) (not significant).

About 50% of patients in the Tramadol Group made comments, whereas in the other two groups, only about 25% of patients commented in the patient diary. The comments of the Tramadol Group were predominantly related to the good analgesia but also to the severity of nausea and dizziness. Tiredness was a very common complaint in all study groups. In response to "suggestions for improvement," many patients commented that patient education should include information about the possibilities of pain persisting more than 3 days, of severe side effects from the analgesic drugs, and about the increased likelihood of tiredness and its implications regarding driving and similar activities.

	Discussion

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Pain after ambulatory hand surgery can be considerable and was adequately controlled with oral analgesics in most patients. There was no hospital admission because of inadequate pain control. However, side effects related to tramadol decreased patient satisfaction.

Tramadol provided the most effective analgesia, as seen by low VAS scores and least requirements of supplemental dextropropoxyphene. As compared with the other two groups, none of the patients in the Tramadol Group required IV morphine analgesia before discharge. These differences were less distinct on the day after surgery. The increased incidence of side effects, particularly postoperative nausea and vomiting, has been reported in other studies with tramadol (6,8–12). Cossmann and Wilsmann (5) reported the frequency of adverse effects in 13,802 patients receiving tramadol for treatment durations of 7 and 90 days. The most frequently reported side effects were nausea (24%–40%), vomiting (9%–17%), dizziness (26%–33%), headache (18%–32%), and sedation (16%–25%). In a randomized, controlled comparison between subcutaneous tramadol and subcutaneous morphine patient-controlled analgesia for postoperative analgesia after major orthopedic surgery, both drugs provided effective analgesia and had a similar side effect profile. The incidence of postoperative nausea and vomiting was increased after tramadol, with 65% of patients complaining of at least one episode of postoperative nausea and vomiting, compared with 40% in the Morphine Group (13).

Metamizol alone provided effective analgesia in 69% of patients on Day 1 and in 85% patients on Day 2. It was associated with consistently better pain scores than acetaminophen but did not reach statistical significance. Satisfaction with the study drug and global satisfaction with pain management was also best in this group. In general, the incidence of side effects after metamizol and acetaminophen was relatively small.

One of the main reasons for performing surgery on an ambulatory basis is the anticipation of minimal postoperative pain, which can be controlled with oral analgesics. However, several studies have shown that the traditional analgesic drugs (acetaminophen, codeine, combination drugs, and NSAIDs) fail to provide adequate analgesia in many patients (1,2). The incidence of inadequately treated postoperative pain at home has not been studied to any great extent but is generally believed to be small. However, certain categories of patients have an increased incidence of moderate to severe postoperative pain. These include patients undergoing orthopedic, urologic, general, and plastic surgery (1,2). There is a need for better oral analgesic drugs, and this need can be expected to increase as improvements in anesthetic and surgical techniques allow more procedures to be performed in the ambulatory setting (14).

This is the first study that compares tramadol and metamizol with the well established acetaminophen for pain relief at home after ambulatory surgery. The analgesic drugs in this study have different mechanisms of effect. Acetaminophen has analgesic and antipyretic effects similar to aspirin, but neither the site nor the mechanism of the analgesic effect of acetaminophen has been clearly defined (3). It is generally thought to be mediated peripherally (15), though evidence suggests a direct action within the central nervous system (16). Tramadol is a centrally-acting analgesic with a weak affinity for µ-opioid receptors. It also modifies pain transmission by inhibiting neuronal noradrenaline and serotonin uptake, as well as stimulating the release of serotonin (7). Many patients in the Tramadol Group commented about better analgesia starting from the second dose. This is consistent with results from several studies showing that tramadol has a slow onset of action (17,18), presumably because the opioid agonist action in humans is mediated through the o-demethylated metabolite MI and not tramadol itself (17,18). Although metamizol was introduced into clinical practice in 1922 and is widely used in more than 100 countries (19), its site and mechanism of analgesic action are not clearly defined. Combined central and peripheral sites of action seem to be involved (20). The analgesic effect of metamizol is correlated with 4-methyl-amino-antipyrine and 4-amino-antipyrine metabolite concentrations (21). The virtually complete bioavailability of metamizol renders the oral route of administration favorable in most cases.

In conclusion, in this double-blinded, randomized trial, three oral analgesics with different mechanisms of action were evaluated for efficacy at home in patients undergoing hand surgery on a day-case basis. None of the study drugs provided adequate analgesia for all patients, as about 40% required rescue analgesia. Tramadol provided good analgesia on the day of surgery, but it was associated with an increased frequency and intensity of adverse effects and consequently the most dissatisfaction. Metamizol and acetaminophen provided good analgesia in about two thirds of patients and did so with a decreased incidence of side effects. Patients should be informed that postoperative pain may last longer than two or three days and that side effects of some analgesic drugs can be considerable. For at-risk patients, routine prescription of take-home rescue analgesics and antiemetics may be necessary. The importance of a follow-up call to detect any problems cannot be overemphasized.

	Acknowledgments

 
The authors wish to acknowledge Ing-Marie Dimgren and Marianne Welamsson for their secretarial assistance.

	References

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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