Tolerance and analgesic efficacy of a new i.v. paracetamol solution in children after inguinal hernia repair

BACKGROUND: A new intravenous (i.v.) formulation of paracetamol and propacetamol (prodrug of paracetamol) were compared to determine tolerance and relative analgesic efficacy during the first 6 h after inguinal hernia repair performed under general anesthesia combined with ilioinguinal block in children. METHODS: A total of 183 ASA I or II in-patients, aged 1-12 years, admitted for unilateral inguinal hernia repair were randomized to receive in a double-blind design either i.v. paracetamol 15 mg.kg(-1) (n = 95) or propacetamol 30 mg.kg(-1) (n = 88) for postoperative pain relief as soon as pain intensity was greater than 30 on a 100 mm visual analog scale. All patients were evaluated for efficacy and tolerance. Efficacy was evaluated between 15 min and 6 h after the start of the 15 min infusion. RESULTS: The most frequently reported adverse event was injection site pain, which was significantly reduced in the new formulation group (i.v. paracetamol 14.7% vs propacetamol 33.0% of children, P = 0.005). No significant difference was obtained between treatments on pain relief (PR), pain intensity difference (PAID) from baseline, and objective pain scale intensity difference (OPSD). Also, treatment effects did not differ significantly for maximum values and weighted sums of PR, PAID (investigator and child rated), OPSD, time to first request for rescue medication, proportion of children requesting rescue medication, and investigators' global treatment satisfaction. CONCLUSION: A single infusion of i.v. paracetamol 15 mg.kg(-1) produced analgesia similar to a single infusion of propacetamol 30 mg.kg(-1) following inguinal hernia repair in children. Paracetamol i.v. 15 mg.kg(-1) was better tolerated at the injection site than propacetamol.     

Double-blind randomized study of tramadol vs. paracetamol in analgesia after day-case tonsillectomy in children

Fifty children (2-9 years) scheduled for tonsillectomy were enrolled in a double-blind randomized prospective study to compare postoperative analgesia provided with propacetamol/paracetamol (acetaminophen) or tramadol. A standard anaesthetic technique was used; each patient received sufentanil 0.25 microg kg(-1) intravenously followed with either i.v. propacetamol 30 mg kg(-1) or tramadol 3 mg kg(-1) before surgical incision. For postoperative analgesia, each child received either tramadol drops (2.5 mg kg(-1)) or paracetamol (acetaminophen) suppositories (15 mg kg(-1)), 6 and 12 h after surgery the first day and three times a day during postoperative days 2 and 3. This dosage of paracetamol is lower than the current recommended dosage, which is 40 mg kg(-1) loading dose followed by 20 mg kg(-1) 8 h(-1). Rescue medication consisted of i.v. diclofenac (1 mg kg(-1)) during the first six postoperative hours and oral ibuprofen (6-9 mg kg(-1)) afterwards. Postoperative pain scores (Children's Hospital of Eastern Ontario Pain Scale) in recovery, numerical pain scale in the ward and at home, and rescue analgesic use were significantly lower in the tramadol group. No serious adverse effects were observed.     

Preoperative rectal diclofenac versus paracetamol for tonsillectomy: effects on pain and blood loss

BACKGROUND: Diclofenac is widely used for postoperative analgesia but the perioperative safety of this drug is controversial because of its effect on platelet aggregation, which might increase blood loss. In a prospective investigator-blinded study the effects of diclofenac and paracetamol on pain and blood loss were compared in patients undergoing tonsillectomy. METHOD: Ninety patients were randomised to receive rectal diclofenac 0.65-1.0 mg x kg(-1) or paracetamol 13-20 mg x kg(-1) preoperatively. Ten patients were excluded after randomisation. Pain was evaluated postoperatively by means of the visual analogue scale and by recording the use of pethidine for rescue analgesia. Perioperative blood loss was estimated from measured intraoperative blood loss; use of drugs to achieve haemostasis, and the incidence of reoperations. RESULTS: Anaesthetic or surgical managements did not differ between the groups, but a significantly longer period of surgery was found in the diclofenac group, 32+/-16 vs. 25+/-11 min (P = 0.024). Pain scores or pethidine consumption were not significantly different between the groups. Intraoperative blood loss was significantly larger in the diclofenac group, 1.9 (1.1-3.1) vs. 1.1 (0.7-2.0) ml x kg(-1) (P = 0.007). CONCLUSION: Preoperative rectal diclofenac offers no advantage over paracetamol with respect to postoperative analgesia in tonsillectomy patients but increases intraoperative blood loss.     

Analgesic efficacy of parenteral paracetamol (propacetamol) and diclofenac in post-operative orthopaedic pain

BACKGROUND: Propacetamol is an injectable pro-drug of paracetamol (acetaminophen) with analgesic and antipyretic activities, especially used in the post-operative period. The aim of this study was to assess the analgesic efficacy and safety of intravenous paracetamol, administered as propacetamol, in comparison with placebo and intramuscular diclofenac in patients with post-operative pain. METHODS: This was a randomized, double-blind, double-dummy study. One hundred and twenty patients with moderate to severe pain following total hip arthroplasty received either two administrations of propacetamol 2 g intravenously, 5 h apart (n = 40), one single administration of diclofenac 75 mg intramuscularly (n = 40) or placebo (n = 40). Efficacy measures were assessed before each drug administration, for the 5 h following each study treatment administration and for the total study duration of 10 h. Safety was assessed by reporting adverse events and changes in vital signs, electrocardiogram (ECG) and biochemical investigations before and 24 h after dosing. RESULTS: Both active treatments were effective and statistically superior to placebo over the whole study period, as indicated by the total pain relief score. No significant differences were found between propacetamol and diclofenac for any measures of analgesic activity. Only minor and common adverse events were reported, with no overall differences between the groups. CONCLUSION: Both active treatments were superior to placebo, and the overall efficacy of two intravenous infusions of propacetamol 2 g (equivalent to 1 g of paracetamol), 5 h apart, was not statistically different from that provided by a single intramuscular injection of diclofenac 75 mg over the first 5 h post-dose and over the total 10-h study period. The safety was good.     

Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery

We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability. IMPLICATIONS: After moderately painful surgical procedures, IV paracetamol, administered as propacetamol, may be an asset in the control of acute postoperative pain.     

Diclofenac and/or propacetamol for postoperative pain management after cesarean delivery in patients receiving patient controlled analgesia morphine

BACKGROUND AND OBJECTIVES: A multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. This study evaluates the postoperative analgesic effects of propacetamol and/or diclofenac in parturients undergoing elective cesarean delivery under spinal anesthesia. METHODS: After randomization, 80 healthy parturients received the following: placebo (group M), 100 mg diclofenac rectally every 8 hours (group MD), 2 g propacetamol intravenously every 6 hours (group MP), or a combination of 2 g propacetamol and 100 mg diclofenac (group MDP) as described above. Drugs were administered for 24 hours after surgery. Postoperative pain was controlled with a patient controlled analgesia pump, using morphine. The visual analog scale (VAS) at rest and on coughing, as well as the morphine consumption, were evaluated at 2, 6, and 24 hours postoperatively. Also, the side effects experienced after undergoing the different regimens were compared. RESULTS: The patients' characteristics did not differ significantly between the 4 groups. VAS score at 2 hours, both at rest and on coughing were lower in group MDP and MD compared with group M (P <.05). At 24 hours, there was still a tendency toward lower pain scores in the groups MDP and MD; however, this difference was only statistically significant at rest between the MDP group and the MP and M groups. Morphine consumption at 2, 6, and 24 hours was lower in the MDP and MD groups compared with the MP and M groups (P <.05). The morphine-sparing effect was higher in groups MDP and MD compared with group MP (57% and 46%, respectively, v 8.2%, P <.05). The incidence of side effects was similar in all groups. However, the power of the study was too low to permit an evaluation of potential side effects. CONCLUSION: Diclofenac after cesarean delivery improves analgesia and has a highly significant morphine-sparing effect. We were unable to demonstrate significant morphine-sparing effect of propacetamol or additive effect of propacetamol and diclofenac in this group of patients.     

Postoperative sensitization and pain after cesarean delivery and the effects of single im doses of tramadol and diclofenac alone and in combination

Combining different analgesic mechanisms can reduce postoperative pain. We investigated postoperative pain and sensory sensitization in a double-blinded, placebo-controlled, randomized, single-dose comparison of the monoaminergic and micro -opioid agonist tramadol, 100 mg, and diclofenac 75 mg given IM in combination or alone in 120 patients who had elective cesarean delivery. The time to first postoperative demand for rescue analgesia, pain, tramadol pharmacokinetics, and electrical sensory thresholds at or distant from the incision were studied. The median time to first rescue (interquartile range) was 197 min (70-1000 min) with tramadol plus diclofenac, 48 min (25-90 min) with tramadol plus placebo, 113 min (35-270 min) with diclofenac plus placebo, and 55 min (30-100 min) with double placebo (tramadol plus diclofenac versus all other groups, P < 0.05). Pain intensity decreased markedly over time in all groups, and time and drug effects were significant (analysis of variance; P < 0.00001). Side effects were similarly minimal with all treatments. Pain thresholds at or distant from the incision increased significantly after surgery only with tramadol plus diclofenac. Preoperative sensory thresholds correlated with postoperative sensory changes (r > 0.53; P < 0.0001). The pharmacokinetics of tramadol and O-desmethyltramadol were unchanged by diclofenac. The combination of tramadol and diclofenac resulted in improved analgesia compared with monotherapy. Only the analgesic combination prevented both primary and secondary hyperalgesia. Preoperative sensory thresholds may allow prediction of postoperative sensitization. IMPLICATIONS: The parenteral combination of tramadol and diclofenac resulted in more prolonged and pronounced postoperative analgesia and reduced sensory sensitization compared with the single drugs, with no increase in side effects.     

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.     

A randomized, placebo-controlled study of rofecoxib with paracetamol in early post-tonsillectomy pain in adults

BACKGROUND AND OBJECTIVE: Effective and early treatment of postoperative pain and nausea have become pivotal for the early discharge of patients after tonsillectomy. Opioid-based analgesia is standard practice but the use of non-steroidal anti-inflammatory drugs is discouraged due to their platelet inhibiting properties. The cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drugs are effective analgesics and do not affect platelet function. We hypothesized that premedication with cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug in addition to paracetamol would provide effective analgesia and decrease opioid consumption during early recovery from tonsillectomy. METHODS: In a randomized, placebo-controlled study of adult tonsillectomy patients (n=40) one group (R-group; n=20) was premedicated with paracetamol 1.5 g and rofecoxib 50 mg and a control group (P-group; n=20) was premedicated with paracetamol 1.5 g and placebo. Morphine was used as rescue medication. Postoperative (24 h) pain scores (0--10), morphine consumption as well as intraoperative blood loss were recorded. RESULTS: We found no overall difference in pain scores between the groups but significantly more patients in the placebo group had pain scores >5 within the first 8 h. The rofecoxib group consumed less morphine during the first 12 h. A lower intraoperative blood loss was observed in the rofecoxib group. CONCLUSION: Our results suggest an early although clinically minor analgesic benefit of the addition of a cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug to paracetamol as premedication for adult tonsillectomy.     

Does 1 or 2 g paracetamol added to ketoprofen enhance analgesia in adult tonsillectomy patients?

Background: We have evaluated whether co-administration of intravenous (i.v.) paracetamol could enhance the analgesic efficacy of ketoprofen (a non-steroidal anti-inflammatory drug or NSAID) in patients undergoing a tonsillectomy.
Methods: This prospective, randomized, double-blinded and placebo-controlled add-on study with three parallel groups included 114 patients, aged 16–50 years, and scheduled for elective tonsillectomy. All patients were given ketoprofen 1 mg/kg i.v. after surgery, followed 5 min later by paracetamol 1 or 2 g i.v., or normal saline as a placebo. The primary outcome measure was the proportion of patients requiring oxycodone for rescue analgesia over the first 6 h (pain score >30/100 mm at rest or >50/100 mm during swallowing) after surgery.
Results: No difference was detected in the proportion of patients receiving oxycodone (31/37 in the paracetamol 1 g group, 29/39 in the paracetamol 2 g group and 30/38 in the ketoprofen-alone group) between the three groups. However, significantly less doses of rescue analgesia were provided in the paracetamol groups than in the ketoprofen-alone group ( P =0.005); among those who required rescue analgesia, 27% less oxycodone was required in the paracetamol 1 g group (80 doses, P =0.023) and 38% less in the paracetamol 2 g group (64 doses, P =0.002) than in the ketoprofen-alone group (106 doses).
Conclusion: Combining paracetamol i.v. with ketoprofen at the end of tonsillectomy did not reduce the proportion of the patients requiring rescue analgesia, but the number of opioid doses was less in the add-on groups.     

Isobolographic Analysis of Interactions between Intravenous Morphine, Propacetamol, and Diclofenac in Carrageenin-injected Rats

Background: It has been suggested that the combination of analgesic drugs may have additive or synergistic effects. In clinical practice, this might allow better analgesia and reduction of side effects.

Methods: The effects of analgesic drugs were studied in a model of acute inflammatory pain in carrageenin-injected rats using the vocalization threshold to paw pressure. A combination of three different intravenous drugs were used: morphine, diclofenac, and propacetamol, a pro-drug of acetaminophen. The dose-response curves were first obtained for each drug alone. The analgesic potencies of the combinations of morphine and diclofenac (ratios, 1:5.66 and 1:10), morphine and propacetamol (ratio, 1:250), and diclofenac and propacetamol (ratio, 1:65.7) were thereafter evaluated and compared with the effects of the drugs alone.

Results: For the two different ratios tested, synergy between diclofenac and morphine was observed only with the higher doses. Propacetamol and morphine or diclofenac and propacetamol combinations were additive for all doses tested.     

Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery

We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6-8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients' global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.     

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.     

Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement

We assessed the analgesic efficacy of IV propacetamol and ketorolac in a double-blinded, placebo-controlled study involving patients undergoing total hip or knee replacement procedures. On the first morning after major joint replacement surgery, 164 patients experiencing moderate-to-severe pain were randomly assigned to receive an IV infusion of propacetamol (2 g), ketorolac (15 or 30 mg), or placebo (saline). Patient-controlled analgesia with morphine was made available as a "rescue" analgesic on patient's request during the 6-h postdosing evaluation period. The median time to onset of analgesia with propacetamol (8 [95% confidence interval 6,10] min) was shorter than ketorolac 15 mg (14 [7,16] min), and placebo (16 [8; not estimable] min) although the differences did not reach statistical significance. However, compared with ketorolac 30 mg, propacetamol had a shorter duration of analgesia (3.5 [2;5.4] vs 6 [3.3; not estimable] h). Analysis of pain intensity and pain relief scores demonstrated that propacetamol produced a significantly greater improvement in pain relief than saline from 45 min until 5 h after the injection. Propacetamol was not significantly different from ketorolac 15 mg and 30 mg with respect to the main analgesic efficacy variables during the 6-h assessment period. The most frequently reported adverse event with propacetamol was injection site pain (28% vs 19% for ketorolac 15 mg, 29% for ketorolac 30 mg, and 10% for placebo, respectively). In conclusion, propacetamol (2 g IV) possesses a similar analgesic efficacy to ketorolac (15 or 30 mg IV) after total hip or knee replacement surgery.     

Paediatric post orchidopexy analgesia—effect of diclofenac combined with ilioinguinal/iliohypogastric nerve block

Summary
When ilioinguinal/iliohypogastric nerve blockade is used to provide postoperative analgesia after paediatric orchidopexy, supplemental analgesia may be required postoperatively. Diclofenac is a nonsteroidal analgesic which produces effective analgesia after tonsillectomy. We examined the effect of combining diclofenac with inguinal field block for post orchidopexy analgesia. Following induction of anaesthesia, group 1 ( n = 25) received ilioinguinal block and rectal diclofenac (2 mg·kg⁻¹) and group 2 ( n = 25) received ilioinguinal block alone. Objective pain scores were assessed for the first three h postoperatively and the incidence of postoperative rescue analgesia, noted. Pain scores were significantly less in group 1 at 45, 60, 90 and 120 min postop ( P < 0.05). The postoperative analgesic requirement was significantly lower in the diclofenac group compared to control ( P < 0.05). A single administration of rectal diclofenac is a simple and effective method of significantly improving analgesia associated with inguinal field block, after paediatric orchidopexy.     

Diclofenac or paracetamol for analgesia in paediatric myringotomy outpatients

This prospective, randomized, double-blind study compared the analgesic efficacy of oral diclofenac resinate 0.5 mg.kg(-1) with paracetamol 15 mg/kg(-1) for control of postoperative pain in paediatric patients for outpatient bilateral myringotomy and tube insertion. Paracetamol, the most commonly used oral analgesic for paediatric patients, was compared with a new palatable syrup formulation of diclofenac. Sixty-three ASA 1 orA SA 2 children aged one year and above were randomly assigned to receive diclofenac (Group A) or paracetamol (Group B). The study drug was given 30 to 60 minutes before induction of anaesthesia. Anaesthesia was induced with either inhalational sevoflurane or intravenous thiopentone. All subjects received intravenous fentanyl 1 microg/kg(-1) intraoperatively. Postoperative pain was assessed by a blinded observer using the CHEOPS score on eye-opening, and then at 10, 30 and 60 minutes. Children with a CHEOPS score > 7 received further fentanyl 1 microg x kg(-1). The number of cases requiring this "rescue" analgesia was recorded. Both groups were comparable in demographics, induction technique, duration of anaesthesia and time between premedication and induction of anaesthesia. Overall, CHEOPS scores were low for both groups at all times and did not differ between the groups at any time. Twenty per cent of the diclofenac group and 27% of the paracetamol group required rescue analgesia (not statistically significant). The efficacy of diclofenac 0.5 mg x kg(-1) and paracetamol 15 mg x kg(-1) as oral analgesic premedication for BMT was comparable in children receiving an anaesthetic which included intraoperative administration of fentanyl 1 microg x kg(-1).     

Intravenous administration of propacetamol reduces morphine consumption after spinal fusion surgery

We sought to determine the analgesic efficacy, opioid-sparing effects, and tolerability of propacetamol, an injectable prodrug of acetaminophen, in combination with morphine administered by patient-controlled analgesia (PCA) after spinal fusion surgery. Forty-two patients undergoing spinal stabilization surgery were randomized into two groups, which were given either an IV placebo or an IV injection of 2 g propacetamol every 6 h for 3 days after surgery. The postoperative opioid analgesic requirement was assessed with a PCA device used to self-administer morphine. Pain relief was evaluated by a visual analog pain scale and by verbal rating scores of pain relief at 8-h intervals for up to 72 h after surgery. The cumulative dose of morphine at 72 h was smaller in the Propacetamol group than in the Placebo group (60.3 +/- 20.5 vs 112.2 +/- 39.1 mg; P < 0.001). The pain scores were significantly lower in the Propacetamol group measured at two intervals of the study, although visual analog scale pain intensity scores were smaller than 3 in both groups. Most patients in the Placebo group obtained a greater degree of sedation on postoperative Day 3 (P < 0.05). This study demonstrates the usefulness of propacetamol as an adjunct to PCA morphine in the treatment of postoperative pain after spinal fusion.     

Analgesic effect of i.v. paracetamol: possible ceiling effect of paracetamol in postoperative pain

BACKGROUND: Despite the widespread use of paracetamol for many years, the analgesic serum concentrations of paracetamol are unknown. Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied. METHODS: Sixty-four women undergoing laparoscopic sterilization were included in a double-blind, placebo-controlled, randomized study. Patients were given i.v. propacetamol 40 mg kg(-1) (group H), 20 mg kg(-1) (group I), 10 mg kg(-1) (group L) or placebo after surgery. Alfentanil was available via patient-controlled analgesia (PCA) during the 4-h postoperative study period. The patients' self-reported pain was registered on the visual analog scale (VAS). A pharmacokinetic model was fitted to the paracetamol data. RESULTS: One to 3 h after injection of propacetamol the alfentanil consumption was significantly (P = 0.01-0.04) higher in the placebo group compared with groups H, I, and L receiving propacetamol. There were no significant differences between the amounts of alfentanil consumed in groups H, I, and L. Initial VAS-scores were moderate (5.4-6.2), and declined significantly (P < 0.0001) over time, with no difference between groups. Paracetamol followed an open two-compartment model with i.v. administration and first order elimination. The estimated concentrations immediately (t = 0) after injection were 56 mg l(-1) (H), 28 mg l(-1) (I) and 14 mg l(-1) (L). CONCLUSION: We showed a significant opioid-sparing effect of paracetamol in the immediate postoperative period. Pharmacokinetic data were in accordance with other studies. Our results suggest that a ceiling effect of paracetamol may be present at i.v. doses of 5 mg kg(-1), i.e. a serum concentration of 14 mg l(-1), which is a lower dose than previously suggested.     

Preoperative diclofenac sodium and tramadol for pain relief after bimaxillary osteotomy.

PURPOSE: The aim of this study was to compare the postoperative analgesic affects of preoperative use of a synthetic opioid tramadol and a nonsteroidal anti-inflammatory drug diclofenac sodium for postoperative pain, with placebo, in patients undergoing bimaxillary osteotomy. PATIENTS AND METHODS: Thirty-six orthognathic surgery patients who underwent both Le Fort I osteotomy in the maxilla and bilateral sagittal split ramus osteotomy in the mandible as bimaxillary osteotomy were randomly allocated into 3 groups via sealed envelope technique. Group T (n = 12), group D (n = 12), and group P (n = 12) received preoperative 50 mg tramadol intramuscularly, 75 mg diclofenac sodium intramuscularly, and saline, respectively. Postoperative pain intensity (visual analog scale, verbal pain score), postoperative opioid consumption with intravenous patient-controlled analgesia, hemodynamic variables, and postoperative complications were compared among the 3 groups. RESULTS: The median number of patient-controlled analgesia demands (n) in group P (34, 28-39) was higher than other groups (group D 14, 11-13; group T 19, 12-25; P = .001). Total tramadol consumption was higher in group P (330 mg, 290-390) compared with group D (260 mg, 190-340; P = .046) and group T (270 mg, 200-330; P = .034). The 3 groups were comparable for the area under the hemodynamic variables time curves. The area under the visual analog scale and verbal pain score curves were lower in group D and group T compared with group P, however, there was no significant difference between group T and group D. CONCLUSIONS: Preoperative diclofenac or tramadol, compared with placebo, effectively decreases postoperative opioid consumption via intravenous patient-controlled analgesia.     

Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery

Postoperative pain management after cardiac surgery has been mainly based on parenteral opioids. However, because opioids have numerous side effects, coadministration of non-opioid analgesics has been introduced as a method of reducing opioid dose. In this prospective, randomized, double-blinded study, we evaluated the efficacy of propacetamol, an IV administered prodrug of acetaminophen (paracetamol), as an adjunctive analgesic after cardiac surgery. Seventy-nine patients scheduled for elective coronary artery bypass grafting were randomized to receive either propacetamol 2 g (n = 40) or placebo (n = 39) IV in 6-h intervals for 72 h. From the time of extubation, patients had access to an opioid (oxycodone) via a patient-controlled analgesia device. Pain was evaluated on a visual analog scale four times daily, whereas respiratory function tests (forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and arterial blood gas measurements) were performed once a day. The prespecified primary efficacy variable (cumulative oxycodone consumption at the end of the 72-h postoperative period) was 123.5 mg (51.3 mg) (mean [SD]) in the propacetamol group and 141.8 mg (57.5 mg) in the placebo group (difference in mean, 18.3 mg = 13%; 95% confidence interval, 6.1-42.7 mg; P = 0.15). Pain scores did not differ between the groups at rest (P = 0.65) or during a deep breath (P = 0.72). The groups were also similar in terms of pulmonary function tests, postoperative bleeding, and hepatic function tests, and no significant differences were noted in the incidences of adverse effects. After completion of the study, apost hoc analysis was also performed analyzing the first 24 h as split into 6-h intervals. This analysis showed a significantly (P = 0.036) smaller consumption of oxycodone in the propacetamol group at 24 h (47.1 mg [20.7 mg] versus 57.9 mg [23.9 mg]; difference in mean, 10.8 mg; 95% confidence interval, 0.7-20.9 mg). In conclusion, propacetamol did not enhance opioid-based analgesia in coronary artery bypass grafting patients, nor did it decrease cumulative opioid consumption or reduce adverse effects within 3 days after surgery. However, post hoc analysis showed that oxycodone requirement was reduced within the first 24 h in the propacetamol group. IMPLICATIONS: This is the first placebo-controlled study to investigate the efficacy of propacetamol as a complementary analgesic to opioids after cardiac surgery. Propacetamol did not enhance analgesia, nor did it decrease cumulative opioid consumption or reduce adverse effects in a dose of 2 g given every sixth hour for 3 days after surgery.