Analgesic efficacy of tramadol/acetaminophen and propoxyphene/acetaminophen for relief of postoperative wound pain.

BACKGROUND/PURPOSE: Weak opioid combined with acetaminophen (APAP) has been proven to provide better analgesic efficacy and cause fewer complications than either drug alone. However, there are questions about whether different opioids, tramadol and propoxyphene, provide similar efficacy or safety. Thus, we investigated Ultracet (37.5 mg tramadol/325 mg APAP) and Depain-X (65 mg propoxyphene/650 mg APAP). The primary aims of this study were to compare the analgesic efficacy and adverse effects of single-dose oral Ultracet versus Depain-X in acute postoperative pain. MATERIALS AND METHODS: This was a randomized, open-label, active-controlled parallel study on patients with postsurgical pain. Sixty patients who sustained moderate postsurgical pain (visual analog scale(3)3 cm) after undergoing implantation of venous access were randomized to two groups to receive either Ultracetor Depain-X for postoperative analgesia. Assessment items included pain intensity and pain relief ratings at the first 4 hours, and adverse events. RESULTS: There were initially 107 patients who were enrolled in this trial, but up to 45 (42.1%) of them were withdrawn during the study. In these 62 patients who complied with treatment (Ultracet: Depain-X = 29: 33), pain relief scale indicated that Ultracet could provide a better analgesic effect than Depain-X provided at 1 hour (p < 0.05). At 4 hours, the pain score in the Ultracet group was significantly lower than that in the Depain-X group (p < 0.05). Adverse events, such as drowsiness, dizziness, and skin itching did not differ in both groups. CONCLUSION: Among patients with mild to moderate postoperative wound pain, single-dose Ultracet can provide slightly better analgesic efficacy than Depain-X in terms of onset and duration. Depain-X is no longer marketed in Europe, America, Taiwan and other countries, therefore, Ultracet can serve as a good substitute for treating postoperative pain.

Sex differences in conscious sedation during upper gastrointestinal panendoscopic examination.

BACKGROUND/PURPOSE: Sex differences in response to noxious stimuli or analgesia have been demonstrated. We investigated sex differences in conscious sedation during upper gastrointestinal panendoscopic examination with regard to drug dose and entropy scores. METHODS: We investigated sex differences in 30 men and 30 women who were undergoing conscious sedation during upper gastrointestinal panendoscopic examination. The drug mixture was prepared as 5 mg midazolam plus 1 mg alfentanil diluted with normal saline to a volume of 10 mL. An initial injection of 4 mL was followed by an additional 1 mL every 1 minute, until the modified Observer Assessment of Alertness and Sedation (OAAS) rating scale was ≤ 3 when the panendoscope was inserted. Further injection was allowed thereafter. Entropy values, including state entropy (SE) and response entropy (RE), were monitored from baseline to full recovery. RESULTS: The volume of mixture needed to achieve an OAAS score of ≤ 3 was significantly lower in men than in women (4.4 ± 0.7 mL vs. 4.8 ± 0.8 mL, p = 0.034). The initial drug demand was not significantly influenced by age, body weight, or body height. The RE and SE values at the time of panendoscope insertion were not significantly different between men and women. The total volume for men was also significantly lower than that for women (5.7 ± 1.1 mL vs. 6.5 ± 1.4 mL, p < 0.01). The lowest RE and SE values during the procedure were not significantly different between men and women. CONCLUSION: Women need more analgesic agents than men during panendoscopic examination. There was no significant difference between men and women with regard to anesthetic depth and response to noxious stimuli, as revealed by similar SE and RE values.

Compatibility and stability of binary mixtures of ketorolac tromethamine and tramadol hydrochloride injection concentrate and diluted infusion solution.

OBJECTIVE: Ketorolac added to tramadol as an injection mixture convenient for clinical use has been shown to be an effective balanced analgesic regimen in alleviating moderate-to-severe pain. However, analytical confirmation of the compatibility and stability of this combination is not available. This study examined the compatibility and stability of this combination. METHODS: Two different mixtures containing ketorolac tromethamine and tramadol hydrochloride were examined: ketorolac (10 mg/mL) and tramadol (33.3 mg/mL) prepared as injection concentrate in ampoule mingled together in the ratio of one ampoule to one ampoule; diluted ketorolac (2 mg/mL) and tramadol (20 mg/mL) prepared in saline infusion solution, with or without pH adjustment. The mixtures were visually inspected for precipitation and color change. Quantitative chemical analysis was performed on days 0, 1, 3 and 7 by high-performance liquid chromatography. RESULTS: When stored at room temperature under ambient light, the ketorolac (10 mg/mL)-tramadol (33.3 mg/mL) injection concentrate and ketorolac (2 mg/mL)-tramadol (20 mg/mL) solution, without pH adjustment and adjusted to pH 5-8, were physico-chemically stable, and neither visible precipitation nor loss of concentration was found. With the ketorolac (2 mg/mL)-tramadol (20 mg/mL) solution adjusted to pH 9, however, precipitation occurred immediately, resulting in a significant loss of tramadol. CONCLUSION: This study suggests that a ready-to-use ketorolac-tramadol mixture, either undiluted or diluted in physiological saline solution, can be prepared, with a shelf life of at least 7 days when stored at room temperature under ambient light.

Combination of low-dose nalbuphine and morphine in patient-controlled analgesia decreases incidence of opioid-related side effects.

BACKGROUND/PURPOSE: The addition of ultra-low-dose naloxone to patient-controlled analgesia (PCA) with morphine reduces opioid-related side effects. Nalbuphine, a mixed opioid agonist-antagonist, may be able to attenuate opioid-related side effects. The goal of the present study was to investigate the effect of combined low-dose nalbuphine and morphine in PCA for postoperative pain control after gynecological surgery. METHODS: This randomized, double-blind, controlled study enrolled 174 female patients who were undergoing total abdominal hysterectomy, myomectomy, or ovarian tumor excision. In the control group, the PCA formula was 1 mg/mL pure morphine. In the study group, the PCA formula was 1 mg/mL morphine and 10 microg/mL nalbuphine (1:100). Numerical rating score, PCA requirement, nausea, vomiting, use of antiemetics, pruritus, use of antipruritics, and opioid-related adverse events were investigated at 1, 2, 4, and 24 hours postoperatively. RESULTS: One hundred and sixty-nine patients completed the study: 86 in the control group and 83 in the study group. The incidence of nausea was lower in the study group (41%) than in the control group (65%). The incidence of vomiting, use of antiemetics, pruritus, and use of antipruritics did not differ between the two groups. The numerical rating pain score and PCA requirements were not significantly different between the two groups. CONCLUSION: Combination of low-dose nalbuphine and morphine in PCA decreases the incidence of opioid-related nausea, without affecting the analgesia and PCA requirement. This novel combination can improve the quality of PCA used for postoperative pain control after gynecological surgery.

Effect of combining ultralow-dose naloxone with morphine in intravenous patient-controlled analgesia: the cut-off ratio of naloxone to morphine for antiemesis after gynecologic surgery.

BACKGROUND/PURPOSE: Admixing an ultralow dose of naloxone with intravenous morphine patient-controlled analgesia (PCA) has been shown to decrease postoperative nausea. However, the cut-off ratio of the naloxone-morphine admixture for antiemetic effects has not been investigated. The purpose of this study was to investigate the cut-off ratio of naloxone-morphine admixture in PCA for antiemesis after gynecologic surgery. METHODS: This double-blind study enrolled 120 female patients who were scheduled for gynecologic surgery under general anesthesia. Patients were randomly allocated to one of three groups (n = 40 for each group). The concentration of naloxone and morphine respectively was 0 microg/mL and 1 mg/mL in group 1, 0.1 microg/mL and 1 mg/mL in group 2 (1:10,000), and 1 microg/mL and 1 mg/mL in group 3 (1:1000). Morphine consumption, verbal rating score of wound pain at rest and with exertion, and morphine-related side effects were investigated at 1, 2, 4 and 24 hours postoperatively. RESULTS: A total of 112 patients completed the study (37 in group 1, 36 in group 2, 39 in group 3). The incidence of nausea during the postoperative 4-24 hours was significantly lower in group 3 than in group 1 (23.1% vs. 56.8%, p < 0.05). Furthermore, the overall incidence of severe nausea was significantly lower in group 3 than in group 1 (2.6% vs. 24.3%, p < 0.05) as was the rescue antiemetic requirements (5.1% vs. 24.3%, p < 0.05). However, there were no significant differences between groups 2 and 1. The pain scores (at rest and with exertion) and 24-hour morphine consumption were not significantly different among the three groups. CONCLUSION: The antiemetic efficacy of ultralow-dose naloxone combined with PCA morphine is limited by a cut-off ratio of naloxone to morphine of 1:10,000.