Early bioavailability of paracetamol after oral or intravenous administration

BACKGROUND: Paracetamol is a peripherally acting analgesic commonly used in multimodal post-operative pain management to reduce the need for more potent analgesics with their unwanted side-effects. The dose and optimal galenical form for achieving analgesic concentrations is not well defined. The primary aim of this pilot project was to study the early bioavailability for two fixed doses of orally administrated paracetamol and one dose of intravenous propacetamol, all of which were given after minor surgery. METHODS: Thirty-five patients undergoing day surgery were divided into five groups, seven patients each. Groups received either 1 g of an ordinary paracetamol tablet, 2 g of an ordinary paracetamol tablet, 1 g of a bicarbonate paracetamol tablet, 2 g of a bicarbonate paracetamol tablet or 2 g intravenously of prodrug propacetamol. We studied the plasma concentration of paracetamol during the first 80 min after administration. RESULTS: Within 40 min, intravenous propacetamol gave a median plasma paracetamol concentration of 85 micromol/l (range 65-161) and decreased thereafter. After oral administration, median plasma paracetamol concentration increased with increasing dose and time, but there were huge inter-individual differences at all time points studied. At 80 min after oral paracetamol the median plasma concentrations were 36 and 129 micromol/l for the 1- and 2-g groups, respectively, with an overall range between 0 and 306 micromol/l. CONCLUSION: Oral administration of paracetamol as part of multimodal pain management immediately post-operatively resulted in a huge and unpredictable variation in plasma concentration compared with the intravenous administration.     

Pediatric intravenous paracetamol (propacetamol) pharmacokinetics: a population analysis

BACKGROUND: The aim of this study was to describe propacetamol pharmacokinetics in children in order to predict concentrations after a standard dosing regimen of propacetamol 30 mg x kg(-1) (15 mg x kg(-1) paracetamol) 6 h. METHODS: A population pharmacokinetic analysis of paracetamol time-concentration profiles (846 observations) from 144 children [postconception age (PCA) 27 weeks-14 years] was undertaken using nonlinear mixed effects models (NONMEM). These data were taken from seven separate studies involving children given intravenous propacetamol. Time-concentration profiles (503 observations) from a further 86 children (PCA: 37 weeks-14 years) given paracetamol elixir orally were included in the analysis to assess relative bioavailability of intravenous propacetamol. RESULTS: A three-compartment (depot, central and peripheral) linear disposition model fitted data better than a two-compartment (depot and central) model. Population parameter estimates (between subject variability, %) were central volume (V2/F(oral)) 24 (55%) l x 70 kg(-1), peripheral volume of distribution (V3/F(oral)) 30 (32%) l x 70 kg(-1), clearance (CL/F(oral)) 16 (40%) l x h(-1) x 70 kg(-1) and intercompartment clearance (Q/F(oral)) 55 (116%) l x h(-1) x 70 kg(-1). Clearance increased from 27 weeks PCA (1.87 l x h(-1) 70 kg(-1)) to reach 84% of the mature value by 1 year of age (standardized to a 70 kg person using allometric '1/4 power' models). Peripheral volume of distribution decreased from 27 weeks PCA (45.0 l x 70 kg(-1)) to reach 110% of its mature value by 6 months of age. Central volume of distribution and intercompartment clearance did not change with age. Between occasions variability for the peripheral volume of distribution (V3/F(oral)) and clearance (CL/F(oral)) were 18.5 and 19.3%, respectively. A rate constant representing hydrolysis of propacetamol to paracetamol (K(a) 96 h(-1)) was size related, but not age related. The relative bioavailability of intravenous propacetamol compared with an oral elixir was 0.5. CONCLUSIONS: A mean paracetamol serum concentration of 10 mg x l(-1) is achieved in children 2-15 years given a standard dose of propacetamol 30 mg x kg(-1) 6 h. This concentration in the effect compartment is associated with a pain reduction of 2.6/10 after tonsillectomy and provides satisfactory analgesia for mild to moderate pain. Clearance is reduced in children less than 1 year of age and the target concentration of 10 mg x l(-1) may be achieved by scaling this standard dose regimen using predicted clearance in this younger age group.     

Pharmacokinetics and antipyretic effects of an injectable pro-drug of paracetamol (propacetamol) in children

Propacetamol is a soluble injectable form of paracetamol, which is quickly hydrolysed after intravenous injection. We report the pharmacokinetic results of this drug in children between 10 months and 14 years of age. Three minutes after an i.v. administration of 15 mgkg^-1 the mean plasma paracetamol concentration was about 25 μgml^-1. In a course of repeated administration of propacetamol, the plasma concentration 3 min after the fourth dose remained at about the same value, showing that there was no accumulation of paracetamol. The pharmacokinetic parameters (half life, total clearance and distribution volume) were similar to those in adults. At 15 mgkg^-1 doses, the antipyretic effect is well-established.     

The analgesic efficacy of an injectable prodrug of acetaminophen in children after orthopaedic surgery

The analgesic efficacy and safety of propacetamol, an injectable prodrug of acetaminophen, (paracetamol) were studied in 87 children (36 boys, 51 girls; age 6–13; mean age 9.5 years) immediately after limb surgery. Using a double-blind, randomized, parallel group design, the effects of a single IV infusion of 30 mg·kg⁻¹ propacetamol (i.e. 15 mg·kg⁻¹ acetaminophen) were compared with a single injection of placebo (PL). Efficacy was assessed on pain scores rated on a four-point verbal scale, a five-point visual scale (faces) and on a four-point relief verbal scale before administration (T0) and 0.25, 0.5, 1, 2, 3, 4, 5, 6 h after administration. At the end the global efficacy was rated by the physician on a five-point verbal scale. Propacetamol was statistically superior to placebo on all assessment criteria. Seven side-effects were recorded: five in the propacetamol group and two in the placebo group. 30 mg·kg⁻¹ propacetamol provided a significantly greater analgesic effect than placebo in children after orthopaedic surgery.     

Analgesic efficacy of diclofenac in combination with morphine and paracetamol after mastectomy and immediate breast reconstruction

BACKGROUND: Breast cancer treatment with mastectomy and immediate breast reconstruction (IBR) is associated with intense pain in the primary post-operative period. The present prospective, placebo-controlled and double-blind study aimed to evaluate the analgesic efficacy of diclofenac, a non-steroid anti-inflammatory drug (NSAID), in combination with paracetamol and opioids. This was done by 64-h assessment of post-operative pain intensity, opioid consumption, blood loss, nausea and tiredness. METHODS: Fifty women selected for mastectomy and IBR with submuscular implants with or without axillary lymph node dissection (ALND) were randomized to receive diclofenac 50 mg x 3 or placebo rectally in addition to oral paracetamol and intravenous opioids delivered using a patient-controlled analgesia (PCA) technique. RESULTS: During the first 20 h post-surgery, patients who received diclofenac experienced significantly less pain when resting than those who received placebo. When moving, a non-significant estimated difference in pain in favour of diclofenac was also noted. Opioid consumption during the first 6 h post-operatively was 34% less with diclofenac than with placebo. Means (SD) were 16.9 (10.3) mg and 25.6 (10.2) mg, respectively (P = 0.007). After 64 h, the difference was no longer statistically significant. Post-operative bleeding was significantly higher with diclofenac than with placebo (P < 0.01). Nausea and tiredness did not differ between the groups. CONCLUSIONS: The addition of NSAID to paracetamol and opioid-PCA reduced opioid consumption and improved pain relief during the first 20 h at rest but was not convincingly effective during mobilization. Post-operative blood loss was higher with diclofenac.     

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.     

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.     

Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection*

In order to compare the morphine-sparing effect, analgesic efficacy and tolerance of nefopam and propacetamol given at their highest recommended doses, 120 patients undergoing elective hepatic resection were randomly assigned to receive postoperative intravenous patient-controlled analgesia with morphine alone, or in combination with nefopam (20 mg.4 h-1) or propacetamol (2 g.6 h-1). Compared with the control group (43 [7-92] mg), median [range] cumulative morphine consumption for 24 h after the study started was halved in the nefopam group (21 [3-78] mg, p <0.001) and 20% lower in the propacetamol group (35 [6-84] mg, p = 0.15). Analgesia was superior in the nefopam group despite the lower morphine consumption. Adverse effects were comparable in the three groups, except for significantly more nausea in the control group (39% vs. 17 and 26% in the nefopam and propacetamol groups, respectively) and more sweating in the nefopam group (17% vs. 0 and 3% in the control and propacetamol groups, respectively). Overall patient satisfaction was better (p < 0.001) in patients given nefopam (97%) than those receiving morphine alone (82%) or propacetamol (74%).     

Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy

BACKGROUND: Diclofenac and paracetamol have different mechanisms and sites of action. Therefore, we tested if their combination is more effective for analgesia after tonsillectomy than either drug alone with respect to rescue analgesic consumption and visual analog scale values. METHODS: The analgesic effects of intravenously administered propacetamol (injectable pro-drug of paracetamol) and diclofenac or a combination on postoperative pain were compared in 71 adult elective tonsillectomy patients in a randomized, double-blind study. After induction of anesthesia the patients received monotherapy with 2 g propacetamol (n = 25) or 75 mg diclofenac (n = 25), or a combined treatment with 2 g propacetamol and 75 mg diclofenac (n = 21) in physiologic saline as an infusion. Postoperatively the propacetamol dosage was repeated twice and diclofenac once on the ward. Oxycodone (0.03 mg kg(-1)) was used as a rescue analgesic by patient-controlled analgesia. RESULTS: On average the patients needed oxycodone 15.3, 13.2 and 10.6 times in the propacetamol, diclofenac and combination groups, respectively (NS). A verbal rating scale and a visual analog scale were employed for assessing post-tonsillectomy pain, nausea and patient satisfaction in all groups. No statistically significant differences were found between the groups. Twelve of the 25 (48%) patients having received propacetamol complained of pain at the cannulation site. CONCLUSION: Combined treatment with propacetamol and diclofenac with the dosages used provided clinically only a minor advantage over monotherapy with propacetamol or diclofenac with respect to postoperative analgesia or the incidence of side-effects in adult tonsillectomy patients.     

Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

Background: The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double‐blind placebo controlled study. Methods: During surgery all infants (6 months–2 years) received a rectal loading dose of 40 mg·kg^?1 paracetamol 2 h before anticipated extubation. On admittance to the pediatric surgical ICU, the children were randomized to receive either a 15 min intravenous infusion of 40 mg·kg^?1 propacetamol, a prodrug of paracetamol, or 20 mg·kg^?1 paracetamol rectally every 6 h. A population pharmacokinetic analysis of the paracetamol plasma concentration time‐profiles was undertaken using nonlinear mixed effects models. The visual analogue scale (VAS) (score 0–10 cm) and COMFORT Behavior scale (score 6–30) were used to monitor analgesia in the 24‐h period following surgery. Results: Twelve infants received intravenous propacetamol and 14 paracetamol suppositories. Paracetamol pharmacokinetics were described according to a two‐compartmental model with linear disposition. Pharmacokinetic parameters were standardized to a 70 kg person using allometric ‘1/4 power’ models. Parameter estimates were: absorption half‐life from the rectum 4.6 h, propacetamol hydrolysis half‐life 0.028 h, clearance 12 l·h^?1·70 kg^?1, intercompartmental clearance 116 l·h^?1·70 kg^?1, central and peripheral volume of distribution 7.9 and 44 l·70 kg^?1, respectively. During the 24‐h study period 22 infants exhibited VAS scores <4 cm, which was considered a cutoff point. On single occasions four patients, two in each group, exhibited a VAS score ≥4 cm. Nine patients in the rectal treatment group and three patients in the intravenous treatment group received midazolam for COMFORT‐B scores exceeding 17 (P < 0.05). Conclusions: Intravenous propacetamol proved to be more effective than rectal paracetamol in infants after craniofacial surgery. Midazolam was more frequently administered to patients receiving paracetamol suppositories, indicating that these children experienced more distress, possibly caused by pain.     

The effect of paracetamol or diclofenac administered before operation on postoperative pain and behaviour after adenoidectomy in small children

We compared the effects of rectally administered diclofenac (12.5 mg) with paracetamol (125 mg) on pre- and postoperative behaviour and the need for supplementary analgesia in 44 children scheduled for adenoidectomy (with or without myringotomy). The study drugs were given in combination with diazepam (0.5 mg.kg-1) about 20 min before the children were taken to the operating theatre. On arrival there, the children who had received diclofenac were significantly quieter (< 0.05), easier to handle (p < 0.01) and cried less (p < 0.05) than those in the paracetamol group. During recovery, children in the diclofenac group needed fewer supplementary doses of intravenous pethidine than those receiving paracetamol (p < 0.001). There were no obvious differences between the groups in intra-operative bleeding (as estimated by the surgeon), or in measured blood loss. No postoperative complications became evident. The pre-operative rectal administration of diclofenac for pain relief after adenotomy is safe and effective.     

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.     

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.     

Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review)

BACKGROUND: Post-operative pain management is usually limited by adverse effects such as nausea and vomiting. Adjuvant treatment with an inexpensive opioid-sparing drug such as ketamine may be of value in giving better analgesia with fewer adverse effects. The objective of this systematic review was to evaluate the effectiveness and tolerability of ketamine administered peri-operatively in the treatment of acute post-operative pain in adults. METHODS: Studies were identified from MEDLINE (1966-2004), EMBASE (1980-2004), the Cochrane Library (2004) and by hand searching reference lists from review articles and trials. The manufacturer of ketamine (Pfizer AS, Lysaker, Norway) provided search results from their in-house database, PARDLARS. Randomized and controlled trials (RCTs) of adult patients undergoing surgery, being treated with peri-operative ketamine, placebo or an active control were considered for inclusion. RESULTS: Eighteen trials were excluded. Thirty-seven trials were included. Twenty-seven out of 37 trials found that peri-operative ketamine reduced rescue analgesic requirements or pain intensity, or both. Quantitative analysis showed that treatment with ketamine reduced 24-h patient-controlled analgesia (PCA) morphine consumption and post-operative nausea and vomiting (PONV). Adverse effects were mild or absent. CONCLUSION: In the first 24 h after surgery, ketamine reduces morphine requirements. Ketamine also reduces PONV. Adverse effects are mild or absent. These data should be interpreted with caution as the retrieved studies were heterogenous and the result of the meta-analysis can not be translated into any specific administration regimen with ketamine.     

The post-operative analgesic effects of a combination of gabapentin and paracetamol in patients undergoing abdominal hysterectomy: a randomized clinical trial

BACKGROUND: The aim of the present study was to compare the effects of a combination of gabapentin and paracetamol with gabapentin alone and placebo on post-operative pain and morphine consumption. METHODS: Seventy-five ASA I-II patients undergoing abdominal hysterectomy were included in the study and randomly divided into three groups. Placebo capsules (Group I, n = 25), 1200 mg of gabapentin (Group II, n = 25), or 1200 mg of gabapentin and 20 mg/kg paracetamol in combination (Group III, n = 25) were administered 1 h prior to surgery. Anaesthesia was standardized for all patients. Non-invasive arterial pressure, heart rate, respiratory rate, peripheral oxygen saturation, morphine consumption, nausea and vomiting, visual analogue scale-pain intensity scores (VAS-PI) and sedation scores were recorded at 1, 2, 4, 6 and 24 h following the operation. RESULTS: Morphine consumption at 24 h was 66.60 +/- 11.49 mg, 42.74 +/- 12.33 mg and 30.50 +/- 11.55 mg, respectively, in groups I, II and III (P < 0.05). Post-operative VAS-PI scores at movement and at rest were decreased with gabapentin and even more with a combination of gabapentin and paracetamol. Post-operative sedation scores were higher in groups II and III during the initial 4 h while these scores were higher in group I at 24 h. CONCLUSIONS: The single dose of gabapentin as well as a combination of gabapentin and paracetamol decreased the opioid requirement and increased the patients' satisfaction post-operatively.     

Effect of paracetamol and coxib with or without dexamethasone after laparoscopic cholecystectomy

Background: Pain after laparoscopic cholecystectomy (LCC) is multifactorial. Effective post-operative pain control is necessary in LCC performed as day-case surgery. We studied the efficacy of paracetamol or valdecoxib with or without dexamethasone after LCC.
Methods: One hundred sixty patients were randomized to four groups of 40 patients. Groups 1 and 3 received parecoxib 40 mg intravenously (IV) during surgery and valdecoxib 40 mg × 1 per os (PO) for 7 post-operative days. Groups 2 and 4 received paracetamol 1 g × 4 IV during surgery and 1 g × 4 PO for 7 days. In addition, Groups 3 and 4 were given dexamethasone 10 mg IV intra-operatively. Propofol and remifentanil were used during surgery. The patients were given oxycodone 0.05 mg/kg IV in phase 1 post-anaesthesia care unit (PACU 1) or 0.15 mg/kg PO in phase 2 post-anaesthesia care unit (PACU 2) as needed to keep visual analogue scale <3/10. The patients were supplied with the study drugs for 7 post-operative days.
Results: Pain intensity, nausea and the need of oxycodone in phase 1 PACU were similar in all groups. Dexamethasone reduced the need of oral oxycodone in phase 2 PACU (7.0 ± 1.0 mg vs. 9.1 ± 1.0 mg, P <0.05). Pain intensity was similar in all groups at home. More patients in the parecoxib/valdecoxib groups needed rescue medication on the 1st post-operative day ( P <0.001) than paracetamol-treated patients.
Conclusion: Paracetamol was as effective as parecoxib/valdecoxib for pain after LCC. Dexamethasone decreased the need of oxycodone in phase 2 PACU. The effect of dexamethasone was similar in paracetamol and parecoxib/valdecoxib patients.     

The effect of gabapentin on post-operative pain following tonsillectomy in adults

Background:  The aim of the present study was to investigate whether a combination of rofecoxib and gabapentin could improve pain relief and reduce opioid requirements, compared with rofecoxib alone, during the first 5 days after tonsillectomy.
Methods:  In a randomized, double-blind, placebo-controlled study, 49 patients received gabapentin 1200 mg pre-operatively, followed by gabapentin 2 × 600 mg on the day of operation and gabapentin 3 × 600 mg for the next 5 days, or placebo. Both groups were given rofecoxib 50 mg daily. In the post-operative care unit, intravenous morphine was administered in doses of 2.5 mg on request. From 4 h to 5 days post-operatively, ketobemidone was offered as escape drug. Pain at rest and during swallowing, and side-effects, were assessed using a four-point verbal rating scale.
Results:  As a result of the global withdrawal of rofecoxib, the study had to be terminated prematurely. This report comprises the results from 22 patients in the gabapentin group and 27 patients in the placebo group. Gabapentin reduced ketobemidone requirements during the first 24 h post-operatively [4.5 mg (standard deviation, 3.0 mg) in the placebo group vs. 2.0 mg (standard deviation, 2.0 mg) in the gabapentin group; P < 0.003]. Gabapentin induced more dizziness ( P < 0.002), gait disturbance ( P < 0.02) and vomiting ( P < 0.05) during days 0–5 than placebo. No other statistically significant differences were observed.
Conclusion:  Gabapentin reduced opioid requirements in the first 24 h after tonsillectomy. The benefits of the reduced opioid intake may be overshadowed by the drawbacks of side-effects.     

Analgesic efficacy of paracetamol and diclofenac in children receiving PCA morphine

We studied 80 children, aged 5-13 yr, who received PCA with morphine after appendicectomy using a standardized tracheal general anaesthetic. All patients received morphine 0.1 mg kg-1 before surgical incision and all had wound infiltration with bupivacaine 1 mg kg-1 at the end of surgery. Patients were allocated randomly to receive postoperative analgesia with PCA morphine alone, morphine plus diclofenac 1 mg kg-1, morphine plus paracetamol 15-20 mg kg-1 or morphine plus a combination of both diclofenac and paracetamol. Cumulative morphine consumption was significantly reduced by concurrent administration of diclofenac but no additive effect of paracetamol was demonstrable with the doses used in the study. Analgesia, as assessed by movement pain scoring, was significantly improved by the addition of diclofenac despite lower morphine consumption. Adverse effects and duration of PCA were comparable in the four groups.