Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery

BACKGROUND: Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled, three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug (propacetamol) and placebo. Propacetamol has been available in many European countries for more than 20 yr. METHODS: After orthopedic surgery, patients reporting moderate to severe pain received either 1 g intravenous acetaminophen, 2 g propacetamol, or placebo at 6-h intervals over 24 h. Patients were allowed "rescue" intravenous patient-controlled analgesia morphine. Pain intensity, pain relief, and morphine use were measured at selected intervals. Safety was monitored through adverse event reporting, clinical examination, and laboratory testing. RESULTS: One hundred fifty-one patients (intravenous acetaminophen: 49; propacetamol: 50; placebo: 52) received at least one dose of study medication. The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h (P < 0.05) and median time to morphine rescue (intravenous acetaminophen: 3 h; propacetamol: 2.6 h; placebo: 0.8 h). Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period: The total morphine doses received over 24 h were 38.3 +/- 35.1 mg for intravenous acetaminophen, 40.8 +/- 30.2 mg for propacetamol, and 57. 4 +/- 52.3 mg for placebo, corresponding to decreases of -33% (19 mg) and -29% (17 mg) for intravenous acetaminophen and propacetamol, respectively. Drug-related adverse events were reported in 8.2%, 50% (most of them local), and 17.3% of patients treated with intravenous acetaminophen, propacetamol, and placebo, respectively. CONCLUSION: Intravenous acetaminophen, 1 g, administered over a 24-h period in patients with moderate to severe pain after orthopedic surgery provided rapid and effective analgesia and was well tolerated.     

Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial

Background: Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy.
Methods: One hundred and sixteen patients were randomly assigned to either group A (paracetamol+placebo × 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexamethasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg × 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation, dizziness, number of vomits and consumption of ondansetron were recorded 2, 4 and 24 h after the operation. P <0.05 was considered statistically significant.
Results: The 24-h morphine consumption and pain score, both at rest and during mobilization, were not significantly different between treatment groups. The mean nausea score ( P =0.002) was reduced in group C vs. A. The number of vomits was significantly reduced in both group B ( P =0.041) and C ( P =0.001) vs. A. Consumption of ondansetron was reduced in group C vs. A and B ( P <0.001). Other side effects were not different between groups.
Conclusion: Combinations of paracetamol and pregabalin, or paracetamol, pregabalin and dexamethasone did not reduce morphine consumption and pain score compared with paracetamol alone for patients undergoing abdominal hysterectomy. Dexamethasone reduced nausea, vomiting and use of ondansetron.     

Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction

Tramadol is a weak centrally acting analgesic and it might provide efficacious postoperative pain relief with minimal sedative effects in the use of intravenous patient-controlled analgesia (PCA). Sixty women scheduled to undergo microvascular breast reconstruction under standard general anaesthesia were enrolled in a study on the performance of patient-controlled analgesia with tramadol or morphine with special emphasis on drug- and technique-related side-effects. Seven patients were re-operated within the same day, leaving 25 patients in the tramadol group and 28 in the morphine group for comparison. When postoperative pain occurred, loading doses of either 10 mg tramadol or 1 mg morphine intravenous increments were administered in a double-blind fashion until the pain control was judged to be satisfactory by the patient. After that the patients received tramadol or morphine by a PCA apparatus (lockout 5 min, tramadol 450 microg kg-1, morphine 45 microg kg-1 bolus). In addition, all patients received 500 mg paracetamol rectally, three times a day. The potency ratio of tramadol to morphine was found to be between 8.5 : 1 (loading) and 11 : 1 (PCA). There was neither a significant difference between the groups in the overall satisfaction of the analgesic medication nor in the visual analogue and verbal rate scales for pain. Women in the tramadol group had more nausea and vomiting during the administration of loading doses (P < 0.05) and more patients in the tramadol group (7) than in the morphine group (3) (NS) wanted to discontinue the PCA therapy before the end of the study due to nausea. Sedation or blurred vision prevented the performance of the psychomotor tests in 22 and 32% of the tramadol and morphine patients, respectively. The remaining patients performed similarly in the Digit Symbol Substitution Test. In women receiving intravenous PCA for analgesia after microvascular breast reconstruction tramadol and morphine provided comparable postoperative analgesia with similar sedative effects. However, tramadol was associated with a disturbingly high incidence of nausea and vomiting.     

Efficacy and Safety of Single and Repeated Administration of 1 Gram Intravenous Acetaminophen Injection (Paracetamol) for Pain Management after Major Orthopedic Surgery

Background: Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled, three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug (propacetamol) and placebo. Propacetamol has been available in many European countries for more than 20 yr.

Methods: After orthopedic surgery, patients reporting moderate to severe pain received either 1 g intravenous acetaminophen, 2 g propacetamol, or placebo at 6-h intervals over 24 h. Patients were allowed "rescue" intravenous patient-controlled analgesia morphine. Pain intensity, pain relief, and morphine use were measured at selected intervals. Safety was monitored through adverse event reporting, clinical examination, and laboratory testing.

Results: One hundred fifty-one patients (intravenous acetaminophen: 49; propacetamol: 50; placebo: 52) received at least one dose of study medication. The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h (P < 0.05) and median time to morphine rescue (intravenous acetaminophen: 3 h; propacetamol: 2.6 h; placebo: 0.8 h). Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period: The total morphine doses received over 24 h were 38.3 +/- 35.1 mg for intravenous acetaminophen, 40.8 +/- 30.2 mg for propacetamol, and 57. 4 +/- 52.3 mg for placebo, corresponding to decreases of -33% (19 mg) and -29% (17 mg) for intravenous acetaminophen and propacetamol, respectively. Drug-related adverse events were reported in 8.2%, 50% (most of them local), and 17.3% of patients treated with intravenous acetaminophen, propacetamol, and placebo, respectively.     

Intravenous patient-controlled analgesia after thoracotomy: a comparison of morphine with tramadol

BACKGROUND AND OBJECTIVE: This study examined the quality of analgesia together with the side-effects produced by tramadol compared with morphine using intravenous patient-controlled analgesia during the first 24 h after thoracotomy. METHODS: Forty-four patients scheduled for thoracotomy were included in the study. Morphine 0.3 mg kg(-1) was given interpleurally 20 min before a standard general anaesthetic. In the postanaesthetic care unit, the patients were randomly allocated to one of two groups to self-administer tramadol or morphine using a patient-controlled analgesia device throughout a 24 h period. The patient-controlled analgesia device was programmed to deliver tramadol 20 mg as an intravenous bolus or morphine 2 mg with a lockout time of 10 min. RESULTS: Mean cumulative morphine and tramadol consumption were 48.13 +/- 30.23 and 493.5 +/- 191.5 mg, respectively. There was no difference in the quality of analgesia between groups. Five (26.3%) patients in the tramadol group and seven (33%) in the morphine group had nausea, and three of the latter patients vomited. The incidence rate of vomiting with tramadol was 5.2%. All vital signs were within safe ranges. Sedation was less in the tramadol group, but not statistically significant. CONCLUSIONS: In this clinical setting, which includes interpleural morphine pre-emptively, postoperative analgesia provided by tramadol was similar to that of morphine at rest and during deep inspiration. Side-effects were slight and comparable between the patients receiving morphine and tramadol.     

Preoperative adjuvant epidural tramadol: the effect of different doses on postoperative analgesia and pain processing

Background: Tramadol is an analgesic with combined opioid agonist and monoamine reuptake blocker properties, which may be useful as a perioperative analgesic and antinociceptive adjuvant.
Methods: The dose-dependent effects of adjuvant preoperative epidural tramadol on postoperative analgesia (pain scores and patient-controlled analgesia (PCA) use) and pain processing (heat pain thresholds) were prospectively studied in a double-blind, randomised, placebo-controlled 5-day trial. Forty patients undergoing knee or hip surgery received anaesthesia with epidural lidocaine and epidural tramadol 20, 50 or 100 mg or placebo as a preoperative adjuvant. Postoperative analgesia was by intravenous PCA tramadol in all patients.
Results: Postoperative pain scores were similar in all groups. The time to first PCA use was shorter, the total dose and duration of PCA use greater, and side-effects more common with 20 mg tramadol than with 100 mg or placebo ( P <0.05). There were no differences in PCA doses required or side-effects between the tramadol 100 mg and placebo treatment groups. Heat pain tolerance thresholds were increased with 100 mg tramadol at 48 h postoperatively compared to baseline and placebo ( P = 0.01).
Conclusions: Preoperative adjuvant epidural tramadol does not improve postoperative analgesia after lidocaine epidural anaesthesia compared to placebo. Tramadol 20 mg results in anti-analgesia and increased side-effects. While tramadol 100 mg depresses postoperative pain-processing, as measured by heat pain tolerance thresholds, this is not reflected in improved clinical pain measures.     

Intravenous Lornoxicam Is More Effective than Paracetamol as a Supplemental Analgesic After Lower Abdominal Surgery: A Randomized Controlled Trial

Background

The aim of this prospective, randomized, double-blind study was to determine the more effective supplemental analgesic, paracetamol or lornoxicam, for postoperative pain relief after lower abdominal surgery.

Methods

Sixty patients scheduled for lower abdominal surgery under general anesthesia were randomly allocated to receive either isotonic saline (control group), intravenous paracetamol 1?g every 6?h (paracetamol group), or lornoxicam 16?mg then 8?mg after 12?h (lornoxicam group). Additionally pain was treated postoperatively with morphine patient-controlled analgesia. Postoperative pain scores measured by the verbal pain score (VPS), morphine consumption, and the incidence of side effects were measured at 1, 2, 4, 8, 12, and 24?h postoperatively.

Results

Morphine consumption at 12 and 24?h was significantly lower in the lornoxicam group (19.25?±?5.7?mg and 23.1?±?6.5?mg) than in the paracetamol group (23.4?±?6.6?mg and 28.6?±?7.6?mg). Both treatment groups had less morphine consumption than the control group (28.5?±?5?mg and 38.1?±?6.6?mg) at 12 and 24?h, respectively. Additionally, VPS was reduced in the paracetamol and the lornoxicam groups compared with the control group both at rest and on coughing. Further analysis revealed that VPS in the lornoxicam group was significantly lower than that in the paracetamol group only during coughing. Drug-related side effects were comparable in all groups.

Conclusions

Lornoxicam is superior to paracetamol for postoperative analgesia after lower abdominal surgery. However, paracetamol could be an alternative supplemental analgesic whenever an NSAID is unsuitable. Trial Registration: clinicaltrials.gov.identifier:NCT01564680.     

Efficacy of intra-articular bupivacaine, ropivacaine, or a combination of ropivacaine, morphine, and ketorolac on postoperative pain relief after ambulatory arthroscopic knee surgery: a randomized double-blind study

BACKGROUND: Effective pain relief is important after diagnostic and therapeutic arthroscopic knee surgery to permit early discharge and improve comfort and mobility at home. The aim of this study was to assess the efficacy of bupivacaine, ropivacaine, or a combination of ropivacaine, morphine, and ketorolac injected intra-articularly for postoperative pain relief after arthroscopic knee surgery. METHODS: Sixty-three healthy patients undergoing knee arthroscopy under local anesthesia (LA) were randomized to receive 1 of the following substances intra-articularly postoperatively: group B: 30 mL of bupivacaine (150 mg); group R: 30 mL of ropivacaine (150 mg); and group RMK: ropivacaine 150 mg, morphine 4 mg, and ketorolac 30 mg in normal saline (total volume 30 mL). Oral paracetamol 1g and tramadol 50 mg were used as rescue drugs. Postoperatively, pain was assessed at rest and movement, and side effects were recorded. The patients were asked to self-assess pain for 7 days and record analgesic consumption as well as activities of daily living (ADLs). Plasma concentration of LA was measured in another 8 patients. RESULTS: All groups had excellent analgesia at 0 and 4 hours postoperatively. Group RMK had significantly lower visual analog pain score at rest at 8 hours and during movement at 8 and 24 hours compared with the other groups (P<.05). Group RMK required less paracetamol and tramadol on day 1 (P<.05), had less sleep disturbances because of pain, more patients were ready to work on days 1 and 2 (P<.05), and were more satisfied on days 1 and 4 to 7. Postoperatively, plasma concentrations of ropivacaine and lidocaine were far below known systemic toxic concentrations in all patients. CONCLUSION: Addition of morphine and ketolorac to ropivacaine intra-articularly enhances analgesic efficacy of LA, reduces postdischarge analgesic consumption, and improves ADLs without increasing side effects after ambulatory arthroscopic knee surgery.     

The addition of a tramadol infusion to morphine patient-controlled analgesia after abdominal surgery: a double-blinded,placebo-controlled randomized trial

In this double-blinded, randomized controlled trial, we tested whether the addition of tramadol to morphine for patient-controlled analgesia (PCA) resulted in improved analgesia efficacy and smaller morphine requirements compared with morphine PCA alone after abdominal surgery in adults. Sixty-nine patients were randomly allocated into two groups, each receiving morphine 1 mg/mL via PCA after surgery. The tramadol group received an intraoperative initial loading dose of tramadol (1 mg/kg) and a postoperative infusion of tramadol at 0.2 mg. kg(-1). h(-1). The control group received an intraoperative equivalent volume of normal saline and a postoperative saline infusion. Postoperatively, tramadol was associated with improved subjective analgesic efficacy (P = 0.031) and there was significantly less PCA morphine use in the tramadol group (P = 0.023). No differences between the groups were found with regard to nausea, antiemetic use, sedation, or quality of recovery (all P > 0.05). We conclude that a tramadol infusion combined with PCA morphine improves analgesia and reduces morphine requirements after abdominal surgery compared with morphine PCA alone. IMPLICATIONS: In this study, we determined whether adding a second pain-killing drug, tramadol, could improve pain relief after major surgery in patients receiving morphine patient-controlled analgesia. We found that patients receiving tramadol had significantly better opinions of their pain relief and used significantly less morphine with no increase in side effects.     

The addition of tramadol to morphine via patient-controlled analgesia does not lead to better post-operative pain relief after total knee arthroplasty

BACKGROUND: Tramadol is used as an analgesic in post-operative pain treatment. Intravenous tramadol is often combined with morphine to achieve better pain relief and less side-effects after orthopaedic surgery. However, the available evidence is insufficient to support this combination. For this reason, we conducted the present non-commercial, randomized, double-blind clinical trial. METHOD: Sixty-three patients with osteoarthritis of the knee, selected for primary total knee arthroplasty (TKA), were randomized to receive saline or tramadol 100 mg/ml intravenously every 6 h during the first post-operative day (total, 400 mg/24 h). All patients had access to morphine via a patient-controlled analgesia (PCA) pump. RESULTS: Neither during the 6 h after the first dose nor during the first post-operative day could we detect any statistically significant difference with regard to pain intensity, sedation and nausea between patients treated with tramadol and the placebo group. However, the withdrawal rate caused by insufficient pain relief was greater in the tramadol group (7/31) than in the saline group (2/32). This difference did not reach statistical significance. In the group of patients who remained in the study for 24 h ('per protocol'), those randomized to receive tramadol had a significantly (P < 0.05) lower morphine consumption (20 mg or 31%) than the placebo group. CONCLUSION: Our study does not support the combination of tramadol and morphine via PCA for post-operative pain relief after primary TKA. In addition, our study indicates that morphine via PCA as the sole means of post-operative analgesia does not provide sufficient pain relief after TKA. Thus, other means of post-operative analgesia should be used following TKA.     

Forty-eight Hours of Postoperative Pain Relief after Total Hip Arthroplasty with a Novel, Extended-Release Epidural Morphine Formulation

Background: Epidural morphine has proven analgesic efficacy in the postoperative period and is widely used. This study evaluated the efficacy of extended-release epidural morphine (EREM; DepoDur; Endo Pharmaceuticals Inc., Chadds Ford, PA; SkyePharma, Inc., San Diego, CA) in providing pain relief for 48 h after surgery.

Methods: Patients (n = 200) scheduled to undergo total hip arthroplasty were randomized to receive a single dose of 15, 20, or 25 mg EREM or placebo. After surgery and after asking for pain medication, patients had access to intravenous patient-controlled analgesia fentanyl for breakthrough pain as needed. Postoperative intravenous patient-controlled analgesia fentanyl use, time to first postoperative fentanyl use, pain intensity at rest and with activity, patient and surgeon ratings of pain control, and adverse events were recorded.

Results: All EREM dosages reduced the mean (+/- SD) fentanyl use versus placebo (510 +/- 708 vs. 2,091 +/- 1,803 [mu]g; P < 0.0001) and delayed the median time to first dose of fentanyl (21.3 vs. 3.6 h; P < 0.0001). All EREM groups had significantly improved pain control at rest through 48 h postdose (area under the curve [0-48 h]) compared with placebo (P < 0.0005). More EREM-treated patients rated their pain control as good or very good compared with placebo (at 24 h: 90 vs. 65%, P < 0.0001; at 48 h: 83 vs. 67%, P < 0.05). No supplemental analgesia was needed in 25% of EREM-treated patients and 2% of placebo-treated patients at 48 h (P < 0.05). The safety profile of EREM was consistent with that of other epidurally administered opioid analgesics.     

Randomized,double-blind,placebo-controlled study of the effect of rectal paracetamol on morphine consumption after abdominal hysterectomy

BACKGROUND: Paracetamol is widely used for postoperative analgesia. The effect is well documented in minor and moderate extensive surgery, but the effect of paracetamol as an adjunct to opioids in major abdominal surgery is less examined. METHODS: Seventy-eight patients scheduled for elective, benign, and abdominal hysterectomy were included in a prospective, randomized, double-blind, parallel group, placebo-controlled study to evaluate the effect of rectal paracetamol in conjunction with intravenous patient-controlled analgesia (PCA) morphine. Paracetamol 1000 mg or placebo suppositories were given four times daily during the 60-h study period. I.V. morphine was administered via a PCA pump, limited to maximum of 12 mg h-1. Morphine consumption, pain and morphine-related adverse effects were recorded. A single-point analysis was comprised of serum concentrations of paracetamol and morphine. RESULTS: Sixty patients were evaluated: 30 in each group. A 16.6% reduction in overall-accumulated morphine consumption in the treatment group (99.6 vs. 83.3 mg) was observed (NS, P = 0.06). Mean paracetamol serum concentration was 0.03 mmol l-1 (range: 0.01-0.06 mmol l-1). None of the patients had a paracetamol concentration within the therapeutic range for antipyretic efficacy. Patients with a higher paracetamol concentration had a lower concomitant morphine (P = 0.025) and morphine-6-glucuronide (P = 0.014) concentration 2 h after paracetamol administration. CONCLUSION: A dosage of rectal paracetamol 1000 mg four times daily is too low, as all displayed a suboptimal serum paracetamol concentration. To study the effect of rectal paracetamol after major surgery we have to increase the dose, as higher serum concentrations of paracetamol may cause lower serum concentrations of morphine.     

Application of sublingual buprenorphine in combination with naproxen or paracetamol for post-operative pain relief in cholecystectomy patients in a double-blind study

In a double-blind, placebo-controlled study in 125 patients undergoing a cholecystectomy, a comparison was made of the quality of post-operative pain relief during 'patient-controlled' intake of sublingual buprenorphine in combination with either rectally administered naproxen 1000 mg/24 h, paracetamol 4000 mg/24 h or a placebo. Results obtained in 97 patients were analysed. Five of these patients needed a rescue medication with morphine hydrochloride intramuscularly because of insufficient pain relief or because of nausea and vomiting. The quality of pain relief, as measured on a four-point scale, was comparable in all three groups throughout the study period and no significant differences became apparent. Only on the day of surgery (day 0) was intake of buprenorphine significantly greater in the placebo group (2.3 tablets/24 h) than in the naproxen and paracetamol groups (1.8 and 1.5 tablets/24 h, respectively). It is concluded that after cholecystectomy 'patient-controlled' intake of sublingual buprenorphine as a sole agent provides acceptable pain relief in about 80% of patients. More elaborate methods, such as intravenous patient-controlled analgesia, might be necessary to achieve good pain relief in the remainder of these patients.     

Comparison of caudal morphine and tramadol for postoperative pain control in children undergoing inguinal herniorrhaphy

OBJECTIVES: We compared the quality and duration of analgesia, the effect on perioperative sevoflurane requirement after a single, presurgical caudal block with either tramadol or morphine in children undergoing inguinal herniorrhaphy. Our study was also designed to evaluate the preemptive analgesic efficacy of morphine administered caudally in children. METHODS: Patients were randomly divided into three groups to receive 2 mg.kg-1 tramadol (group T, preemptive group) or morphine sulphate 0.03 mg.kg-1 (group M, preemptive group). The patients in control group (group C, postincisional group) received morphine sulphate 0.03 mg.kg-1 at the end of surgery, caudally. Cardiorespiratory data, sedation and pain were recorded for 24 h following recovery from anaesthesia. RESULTS: There were no differences between the three groups in baseline blood pressure or heart rate; or duration of anaesthesia, surgery. The inhaled sevoflurane concentration was significantly lower in group M and group T than in the control group. The quality and duration of postoperative pain relief did not differ between the three groups. There were no intergroup differences in postoperative nausea, vomiting, or other complications. CONCLUSION: Caudal tramadol (2 mg.kg-1) provided reliable postoperative analgesia similar to caudal morphine (0.03 mg.kg-1) in quality and duration of pain relief in our study children who were undergoing herniorrhaphy. We also concluded that presurgical caudal morphine or tramadol reduced perioperative sevoflurane requirements and either presurgical or postsurgical caudal morphine did not make any difference to postoperative analgesia.     

Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation

BACKGROUND: Epidural morphine has proven analgesic efficacy in the postoperative period and is widely used. This study evaluated the efficacy of extended-release epidural morphine (EREM; DepoDur; Endo Pharmaceuticals Inc., Chadds Ford, PA; SkyePharma, Inc., San Diego, CA) in providing pain relief for 48 h after surgery. METHODS: Patients (n = 200) scheduled to undergo total hip arthroplasty were randomized to receive a single dose of 15, 20, or 25 mg EREM or placebo. After surgery and after asking for pain medication, patients had access to intravenous patient-controlled analgesia fentanyl for breakthrough pain as needed. Postoperative intravenous patient-controlled analgesia fentanyl use, time to first postoperative fentanyl use, pain intensity at rest and with activity, patient and surgeon ratings of pain control, and adverse events were recorded. RESULTS: All EREM dosages reduced the mean (+/- SD) fentanyl use versus placebo (510 +/- 708 vs. 2,091 +/- 1,803 microg; P < 0.0001) and delayed the median time to first dose of fentanyl (21.3 vs. 3.6 h; P < 0.0001). All EREM groups had significantly improved pain control at rest through 48 h postdose (area under the curve [0-48 h]) compared with placebo (P < 0.0005). More EREM-treated patients rated their pain control as good or very good compared with placebo (at 24 h: 90 vs. 65%, P < 0.0001; at 48 h: 83 vs. 67%, P < 0.05). No supplemental analgesia was needed in 25% of EREM-treated patients and 2% of placebo-treated patients at 48 h (P < 0.05). The safety profile of EREM was consistent with that of other epidurally administered opioid analgesics. CONCLUSIONS: EREM provided significant postoperative pain relief over a 48-h period after hip surgery, without the need for indwelling epidural catheters.     

Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery

BACKGROUND: This study tested the hypothesis that an injectable cyclooxygenase (COX)-2-specific inhibitor will be at least as effective and well tolerated as a COX-nonspecific conventional nonsteroidal antiinflammatory drug (NSAID) by comparing the analgesic efficacy and tolerability of one intravenous dose of parecoxib sodium, an injectable prodrug of the novel COX-2-specific inhibitor, valdecoxib, with ketorolac and placebo in postoperative laparotomy surgery patients. Intravenous morphine, 4 mg, was studied as a positive analgesic control. METHODS: In this multicenter, double-blinded, placebo-controlled study, women experiencing moderate-to-severe pain on the first day after abdominal hysterectomy or myomectomy received one intravenous dose of parecoxib sodium, 20 or 40 mg, ketorolac, 30 mg, morphine, 4 mg, or placebo. Analgesic efficacy and tolerability were evaluated for 24 h postdose or until patients, whose pain was not adequately controlled, opted to receive rescue analgesia. RESULTS: Two hundred two patients were enrolled. All treatment groups had comparable demographics and baseline pain status. All active treatments had an equally rapid time to onset of analgesia (10-23 min). Overall, each parecoxib sodium dose and ketorolac were significantly superior to morphine and placebo for most measures of analgesic efficacy at most time points, including a significantly longer (two- to threefold) time to rescue analgesia (P 相似文献   

Comparison of the analgesic efficacy and respiratory effects of morphine, tramadol and codeine after craniotomy

Pain after craniotomy remains a significant problem. The effect of morphine and tramadol patient-controlled analgesia (PCA) on arterial carbon dioxide tension is unknown in patients having such surgery. Sixty craniotomy patients were randomly allocated to receive morphine PCA, tramadol PCA or codeine phosphate 60 mg intramuscularly. Baseline values of pain score (0-10), sedation and arterial carbon dioxide tension were recorded at the time of first analgesic administration and at 30 min, 1, 4, 8, 12, 18 and 24 h. Patient satisfaction was assessed at 24 h. There were no differences in arterial carbon dioxide tension or sedation between groups at any time, but in all three groups some patients had rises greater than 1 kPa. Morphine produced significantly better analgesia than tramadol at all time points (p < 0.005) and better analgesia than codeine at 4, 12 and 18 h. Patients were more satisfied with morphine than with codeine or tramadol (p < 0.001). Vomiting and retching occurred in 50% of patients with tramadol, compared with 20% with morphine and 29% with codeine.     

Evaluation of the pharmacokinetic profile and analgesic efficacy of oral morphine after total hip arthroplasty

BACKGROUND AND OBJECTIVE: Oral morphine may be useful for postoperative pain relief, but few studies have tested its use after in-hospital surgery. METHODS: We evaluated clinical efficacy and the pharmacokinetic parameters of oral morphine after total hip arthroplasty. We recruited 60 patients who had total hip arthroplasty under general anaesthesia. The patients were randomized to receive placebo, 10 mg morphine sulphate or 20 mg morphine sulphate orally every 4 h for 24 h. The oral administration was started 3 h after the morphine-loading dose in the Post Anaesthesia Care Unit and then patients used intravenous morphine patient-controlled analgesia for 24 h. Pain score at rest (scored by patients on a visual analogue scale), sedation, nausea, vomiting and urinary retention were monitored. In 11 additional total hip arthroplasty patients, we determined the pharmacokinetics of morphine and its metabolites after oral administration of 20 mg morphine sulphate every 4 h for 16 h. RESULTS: The amount of morphine administered via patient-controlled analgesia over 24 h was reduced in the 20-mg group compared with that in the placebo group (19.0 +/- 2.7 mg vs. 33.0 +/- 5.5 mg; P = 0.03). No significant morphine-sparing effect was observed in the 10-mg group. Pain scores and side-effects were similar in all groups. The pharmacokinetic study revealed a limited and slow absorption of morphine. CONCLUSION: Despite a limited absorption of oral morphine postoperatively, high doses of oral morphine have a significant analgesic effect after total hip arthroplasty.     

Low-dose ketamine failed to spare morphine after a remifentanil-based anaesthesia for ear, nose and throat surgery

BACKGROUND: Ketamine has been claimed to prevent acute opioid tolerance and hyperalgesia following acute exposure to opioids and its use has been proposed to decrease postoperative morphine consumption. METHODS: We conducted a randomized, double-blind, controlled study to evaluate the effect of intravenous (i.v.) ketamine on postoperative pain for 48 h after major ear, nose and throat (ENT) surgery. Thirty-one patients received i.v. ketamine 0.15 mg kg(-1) before induction and 2 microg kg(-1) min(-1) during anaesthesia, and 31 patients were administered placebo in a similar manner. Anaesthesia was standardized with remifentanil and propofol, but without nitrous oxide. Standardized postoperative analgesia included paracetamol, methylprednisolone and morphine administered via a patient controlled analgesia (PCA) device. RESULTS: Intra-operative remifentanil consumption was not different between the ketamine group (0.25 +/- 0.07 microg kg(-1) min(-1)) and the control group (0.22 +/- 0.07 microg kg(-1) min(-1)). In the postoperative period, both groups experienced an identical pain course evolution. Cumulative morphine consumption was not significantly different between groups: at 24 h it was 33.3 +/- 14.9 with ketamine and 31.9 +/- 15.3 mg in controls, at 48h it was 40.4 +/- 20.6 mg with ketamine and 42.5 +/- 25.9 mg in controls. CONCLUSION: Low-dose ketamine added to a remifentanil-based propofol anaesthesia did not reduce morphine consumption after major ENT surgery.     

Perioperative dextromethorphan reduces postoperative pain after hysterectomy.

We studied the effect of dextromethorphan, an N-methyl-D-aspartate antagonist, on analgesic consumption and pain scoring after abdominal hysterectomy. In this double-blinded study, 50 patients were randomized into two groups. Group DM was given oral dextromethorphan 40 mg with their premedication, then 40 mg three times per day for the next 2 days. Group P received placebo at identical times. Postoperative analgesic requirements were assessed using a patient-controlled analgesia system and subsequent oral analgesic intake using a set protocol. Pain was assessed at rest and on movement using a visual analog scale 4, 24, 48, and 72 h after the operation. Median pain scores at rest were significantly lower at 48 and 72 h and also for the sum of all resting pain scores. Mean morphine consumption was less in Group DM (1.1 vs 1.5 mg/h; P = 0.054). Usage of oral diclofenac, given every 8 h as needed, did not differ between groups, but consumption of codydramol (paracetamol 500 mg and dihydrocodeine 10 mg) was significantly less in Group DM. We conclude that the use of oral dextromethorphan has an analgesia-sparing effect and some beneficial effects on pain scoring at rest after abdominal hysterectomy. Implications: Patients given dextromethorphan before and after surgery had a significant reduction in some pain scores at rest, but not on movement. There was a trend to lower morphine requirements in the first 24 h. Over the next 48 h, oral analgesic usage was significantly reduced.