Postoperative pain relief; a new approach: narcotics compared with non-steroidal anti-inflammatory drugs.

The pain relief provided by regular intramuscular diclofenac and on demand intramuscular papaveretum was compared over a 48 h postoperative period in 114 patients undergoing total hip replacement. The study was of a randomised, single-blind, between-group design. Patients were assessed by a surgeon, physiotherapist and nursing staff. Diclofenac was more effective than papaveretum in pain control (P less than 0.001), wound tenderness (P less than 0.01), awareness (P less than 0.001) and mobilisation (P less than 0.01). Wound drainage (P greater than 0.05) and wound oedema (P greater than 0.05) were not significantly different in the two treatments. Gastrointestinal complications were encountered in both groups; two patients on diclofenac had to be withdrawn because of them. The use of diclofenac given as a postoperative analgesic is rewarding, particularly in patients undergoing musculoskeletal procedures. Patients will be more comfortable and will mobilise better during their whole postoperative course.     

Nonsteroidal antiinflammatory drugs for postthoracotomy pain. A prospective controlled trial after lateral thoracotomy.

Diclofenac (Voltarol) as an adjunct to papaveretum for pain relief was examined by a prospective, randomized trial in 44 patients who had lateral thoracotomies. Patients given diclofenac, 75 mg intramuscularly twice daily, required less papaveretum in the first 3 days after operation (p less than 0.005) and had lower pain scores on a visual analog scale on all 5 postoperative days (p = 0.02 to less than 0.001); their respiratory vital capacity on the first postoperative day was also significantly higher (p less than 0.02). Diclofenac is a useful adjunct in the management of postthoracotomy pain.     

Dextromethorphan reduces immediate and late postoperative analgesic requirements and improves patients' subjective scorings after epidural lidocaine and general anesthesia

Central N-methyl-D-aspartate receptors modulate postoperative pain. We compared the effects of preincision oral dextromethorphan (DM), an N-methyl-D-aspartate receptor antagonist, on postoperative IV patient-controlled analgesia morphine demand and on subjective variables in 80 patients undergoing lower-body procedures who were randomly assigned to epidural lidocaine (LA; 16 mL, 1.6%) or general anesthesia (GA). The patients were premedicated 90 min before surgery with placebo or DM 90 mg (20 patients per group) in a double-blinded manner. Postoperative IV patient-controlled analgesia morphine administration started when subjective pain intensity was > or =4 of 10 (visual analog scale) and lasted 2 h. Observation continued up to 3 days, during which patients could use diclofenac. LA-DM and GA-DM patients required 45%-50% less morphine and diclofenac compared with their placebo counterparts (P < 0.001). However, GA-DM patients made twice as many attempts to self-administer morphine as LA-DM patients (P = 0.005). Eight LA-DM versus two GA-DM patients (P < 0.01) used no morphine or diclofenac. All DM patients experienced significantly (P < 0.001) less pain, were less sedated, and felt better than their placebo counterparts; however, compared with placebo, DM improved subjective scorings in the GA patients more significantly (P < 0.05) than in the LA patients. We conclude that oral DM 90 mg in patients undergoing surgery under LA or GA reduces morphine and diclofenac use by approximately 50% in the immediate and late postoperative period compared with placebo. Subjectively scored levels of pain, sedation, and well-being were better as well.     

A comparison of rectal diclofenac with intramuscular papaveretum or placebo for pain relief following tonsillectomy

A controlled investigation was conducted to compare the effectiveness of diclofenac and papaveretum in the prevention of pain and restlessness after tonsillectomy in children. Sixty children between 3 and 13 years of age were randomly allocated to receive rectal diclofenac 2 mg/kg, intramuscular papaveretum 0.2 mg/kg or no medication immediately after induction of anaesthesia. Pain and appearance were assessed 1, 3 and 6 hours postoperatively, and the following morning. The assessments were double-blind and performed by the same observer. No significant differences in postoperative pain were found between the groups at any time. The use of diclofenac was associated with a significantly more rapid return to calm wakefulness and had significantly less effect upon respiratory rate. Consumption of paracetamol on the day of operation was significantly less in the diclofenac group. Diclofenac may offer advantages compared to papaveretum with regard to safety and convenience for use in the treatment of pain after tonsillectomy in children.     

Dyloject, a novel injectable diclofenac formulation, offers greater safety and efficacy than voltarol for postoperative dental pain

BACKGROUND AND OBJECTIVES: Voltarol for injection (a diclofenac sodium formulation employing polyethylene glycol and benzyl alcohol [PG-BA] as excipients) is marketed in Europe but not in North America. A suspension, PG-BA diclofenac sodium, requires preparation for each patient and slow IV infusion to minimize venous irritation. Dyloject, a novel diclofenac formulation, employs hydroxypropyl beta-cyclodextrin (HPbetaCD) to solubilize diclofenac in a small volume. We compared the efficacy and safety of an IV HPbetaCD diclofenac sodium bolus, a 30-minute PG-BA diclofenac sodium infusion, and placebo in post-molar extraction pain. METHODS: A total of 155 adult patients were randomized to receive HPbetaCD diclofenac sodium 75 mg, PG-BA diclofenac sodium 75 mg, or placebo. Primary endpoints were superiority of HPbetaCD diclofenac sodium to placebo and noninferiority of HPbetaCD diclofenac sodium to PG-BA diclofenac sodium with respect to total pain relief over 4 hours (TOTPAR4) on a 0 to 100-mm visual analog scale (VAS). Secondary endpoints included categorical TOTPAR4, VAS and categorical TOTPAR up to 8 hours, other measures of pain intensity and relief, patient global evaluation, and time to rescue medication. RESULTS: HPbetaCD diclofenac sodium had efficacy superior to both placebo and PG-BA diclofenac sodium. At 15 minutes, more patients given HPbetaCD diclofenac sodium than PG-BA diclofenac sodium reported 30% reduction in pain intensity (52% vs. 21%, P = .0022). Both diclofenac products had a 6-hour duration of effect and were well tolerated. Patient global evaluations of HPbetaCD diclofenac sodium were high, superior to placebo, and similar to PG-BA diclofenac sodium. The adverse event (AE) incidence was similar for HPbetaCD diclofenac sodium and PG-BA diclofenac sodium, except that in the current trial and in integrated safety results from the present and prior studies, phlebitis was more common with PG-BA diclofenac sodium. No cardiac or renal AEs or gastrointestinal bleeding were reported or observed. CONCLUSIONS: IV bolus HPbetaCD diclofenac sodium produced analgesia more quickly than, and with equal duration as, the 30-minute PG-BA diclofenac sodium infusion. Pooled data on thrombophlebitis from the present investigation and our prior studies of the novel formulation indicate this adverse effect is less frequent and less severe with HPbetaCD diclofenac sodium than with PG-BA diclofenac sodium.     

Transdermal diclofenac patchvs eutectic mixture of local anesthetics for venous cannulation pain

PURPOSE: To compare the efficacy and side effects of transdermal diclofenac patch with eutectic mixture of local anesthetic (EMLA) cream in attenuating venous cannulation pain. METHODS: Adult ASA I or II patients undergoing elective surgery were randomly divided into three groups of 150 each. Group 1 (Control) patients received a placebo patch; Group 2 (EMLA) patients received EMLA cream; Group 3 (Diclofenac) patients received a transdermal diclofenac patch. The patches were applied at the proposed venous cannulation site 60 min prior to cannulation and pain resulting from an 18G cannula was assessed on an ten-point visual analogue scale (VAS). The cannulation site was observed for blanching, erythema, induration and edema for up to 24 hr. RESULTS: The incidence of venous cannulation pain was 100% in the control group, as compared to 37% and 48% of patients who experienced pain in the EMLA (P = 0.001) and diclofenac (P = 0.001) groups, respectively. The severity of venous cannulation pain [median (VAS) with interquartile ranges] was also higher in the control group: 6 (3) as compared to VAS sores of 0 (1) and 0 (2) in the EMLA (P = 0.001) and diclofenac (P = 0.001) groups. Blanching occurred with greater frequency in the EMLA group compared with the diclofenac (P = 0.001 at six hours) and placebo groups (P = 0.001 at six hours). Erythema, induration and edema were reduced in the diclofenac group compared with the EMLA (P = 0.001 for all comparisons) and placebo groups (P = 0.04 for edema at six hours and P = 0.001 for other comparisons). CONCLUSION: Transdermal diclofenac patch and EMLA are equally effective in reducing venous cannulation pain, but signs of erythema, induration and edema are less frequently observed with the transdermal diclofenac patch.     

Intravenous diclofenac sodium Does its administration before operation suppress postoperative pain?

Intravenous diclofenac sodium was evaluated in a double-blind randomised trial relative to intramuscular diclofenac, intravenous fentanyl, and intramuscular placebo in 160 patients undergoing extraction of impacted lower third molar teeth. The test drug was administered before operation in an attempt to alleviate postoperative pain. A 10-cm visual analogue scale was used to assess pain at 30 minutes and one day after surgery, if the patients stayed overnight. Patients who received intravenous diclofenac had significantly less pain than the other groups 30 minutes after operation. They also had significantly less pain one day after surgery than the placebo or opioid groups, but not less than the intramuscular diclofenac group. Capillary bleeding time, in comparison with placebo, was significantly prolonged after the use of intramuscular diclofenac, and a similar but nonsignificant trend was observed in the intravenous diclofenac group. No problems were encountered with excessive bleeding in any group.     

Combined pre-incisional oral dextromethorphan and epidural lidocaine for postoperative pain reduction and morphine sparing: a randomised double-blind study on day-surgery patients

The reduction in acute pain perception following dextromethorphan has previously been investigated in patients undergoing general anaesthesia. This random and double-blind study examined the effects of pre-incisional oral dextromethorphan on postoperative pain and intravenous patient-controlled morphine demand in 60 day-surgery patients undergoing lower body surgery under lidocaine (1.6%-16 ml) epidural anaesthesia after receiving placebo, 60 or 90 mg dextromethorphan, 90 min pre-operatively. Postoperative pain was scored on a visual analogue scale from 1 to 10. In-hospital observation continued for 6 h and for 3 days at home; diclofenac was available throughout. Dextromethorphan-treated patients reported significantly (p < 0.05) less pain and sedation, and felt better. Patients who received dextromethorphan 90 mg had significantly (p < 0.05) lower heart and respiratory rates than those who received 60 mg. Medicated patients required half the morphine and diclofenac of placebo patients: 38% of patients who received 90 mg and 21% who received dextromethorphan 60 mg used no morphine or diclofenac whatsoever, a previously unreported finding.     

Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults?

We have compared the analgesic and opioid sparing effect of three i.v. non-steroidal anti-inflammatory drugs with placebo in a randomized, double-blind, placebo-controlled study in 80 adult patients after elective tonsillectomy. A standard anaesthetic was used. After induction of anaesthesia, patients received ketoprofen 100 mg, diclofenac 75 mg or ketorolac 30 mg by i.v. infusion over 30 min. Patients in the placebo group received saline. Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic. Patients in the ketoprofen group requested 32% less opioid and patients in the diclofenac and ketorolac groups 42% less opioid than those in the placebo group (P < 0.05). There were one, two and six patients in the placebo, diclofenac and ketorolac groups, respectively, but none in the ketoprofen group, who did not request opioid analgesia during the study (P < 0.05, ketorolac vs placebo and ketoprofen). Visual analogue pain scores were similar in all groups. Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group. The incidence of nausea was 44-54%. There were no differences in the incidence of other adverse reactions. We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy.      

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.     

The perioperative effects of oral premedication in children

The pre- and postoperative effects of oral diazepam (0.5 mg/kg), trimeprazine (4 mg/kg), pentobarbitone (3 mg/kg) and a placebo were compared in a randomized double-blind clinical trial in 149 children, aged one to ten years, undergoing adenotonsillectomy. The anaesthetic was standardised and each patient received intraoperative intramuscular papaveretum (0.3 mg/kg). Preoperative sedation was assessed in the ward before transfer onto the theatre trolley, on leaving the ward, on arrival on the theatre floor, on arrival in the induction room and on induction of anaesthesia. There was no significant difference in sedation between the four drug groups except for the placebo group which had a significantly greater unsatisfactory rating at the stage of induction of anaesthesia (P = 0.001). There were no differences in waking times between the diazepam, pentobarbitone and placebo groups, but the trimeprazine group's waking times were significantly prolonged (P less than 0.001). However, the trimeprazine group exhibited significantly less distress in the recovery unit (P = 0.02) and had half the incidence of vomiting (P less than 0.001) than did the other premedication groups.     

Rectal paracetamol has a significant morphine-sparing effect after hysterectomy

We have evaluated the morphine-sparing effect of rectal paracetamol during the first 24 h after abdominal hysterectomy in a placebo- controlled, double-blind study. We studied 72 patients receiving patient-controlled analgesia (PCA) with i.v. morphine after a standardized anaesthetic, allocated randomly to receive rectal paracetamol 1.3 g, diclofenac 50 mg or placebo, after wound closure and at 8 and 16 h. Suppositories were blinded by the hospital pharmacy. Study violations excluded data from seven patients. Patient data, morphine doses during anaesthesia and recovery, and sedation and nausea scores were comparable. Mean morphine consumption during PCA was 35.0 (SD 20.4) mg, 32.7 (27.4) mg and 54.9 (28.3) mg in the paracetamol (n = 24), diclofenac (n = 20) and placebo (n = 21) groups, respectively (P < 0.05). Morphine sparing during PCA for paracetamol and diclofenac (36% vs 40% over 24 h) was significant from 4 h. Global scores of average pain over 24 h were lower after diclofenac compared with paracetamol (P < 0.01) and placebo (P = 0.08). We conclude that rectal paracetamol was an efficacious adjuvant analgesic after regular dosing.      

Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation.

Ninety-six women undergoing laparoscopic tubal ligation were randomized to receive intravenously either 0.2 or 0.4 microgram/kg of dexmedetomidine, 60 micrograms/kg of oxycodone, or 250 micrograms/kg of diclofenac for postoperative pain in a double-blind study design. The study drugs were administered in the recovery room for moderate or severe pain and were repeated until pain subsided or disappeared. In the group receiving diclofenac, 83% of the patients required analgesic supplementation with morphine. This contrasted (P less than 0.01) with 33% of the patients receiving either oxycodone or the higher dose of dexmedetomidine. After the first dose of oxycodone was injected, the visual analogue scale for pain (0%-100%) was reduced from 58% to 33%, whereas corresponding pain relief was only achieved after the third injection of 0.4 microgram/kg of dexmedetomidine. Repeated doses of 0.2 microgram/kg of diclofenac or dexmedetomidine did not reduce the visual analogue scale value by more than 17%. More sedation was seen with the higher dose of dexmedetomidine than with either diclofenac or oxycodone (P less than 0.001). Both doses of dexmedetomidine decreased heart rate when compared with diclofenac (P less than 0.001). In the group given 0.4 microgram/kg of dexmedetomidine, 33% of the patients required atropine for bradycardia. The authors conclude that after laparoscopic tubal ligation, intravenously administered dexmedetomidine relieves pain and reduces opioid drug requirement but is attended by sedation and a high incidence of bradycardia.     

Comparison of the opioid-sparing efficacy of diclofenac and ketoprofen for 3 days after knee arthroplasty

BACKGROUND: Comparative postoperative non-steroidal anti-inflammatory drug (NSAID) studies in orthopedic patients have usually been restricted in time to the first postoperative day. The opioid-sparing effect of NSAIDs may be beneficial postoperatively as long as pain otherwise restricts ambulation and rehabilitation. We therefore compared the analgesic efficacy of the maximum recommended doses of diclofenac and ketoprofen for 3 days after knee arthroplasty. METHODS: We studied 64 knee arthroplasty patients, operated on under spinal anesthesia. In a randomized, double-blind and placebo-controlled fashion, the patients received either i.v. diclofenac 75 mg (n = 24), ketoprofen 100 mg (n = 24) or saline (n = 16) in the recovery room, followed by oral diclofenac 150 mg/day, ketoprofen 300 mg/day or placebo, respectively, for 3 days, supplemented by patient-controlled analgesia (PCA) with i.v. oxycodone. RESULTS: The mean consumption of oxycodone during the first, second and third study days was 45.3, 22.3 and 15.2 mg in the diclofenac group, 43.5, 37.5 and 21.8 mg in the ketoprofen group, and 61.2, 45.9 and 36.1 mg, respectively, in the placebo group. Oxycodone consumption was significantly lower (P < 0.05) in the ketoprofen group than in the placebo group in the postoperative period 13-24 h and 61-72 h. Diclofenac was superior to placebo in the postoperative period 25-48 h (P < 0.01), 49-60 h (P < 0.05) and to ketoprofen at 49-60 h (P < 0.05). During administration of diclofenac on days 1-3 and ketoprofen on day 2, the mean pain scores (VAS) were lower than in the placebo group (P < 0.05). Six patients had difficulties in operating the PCA device. There were no differences in blood loss. CONCLUSION: We conclude that in the first day after knee arthroplasty (13-24 h), ketoprofen exerted an opioid-sparing effect. After day 1 (25-60 h), with the doses used, diclofenac proved to be better than placebo, whereas ketoprofen was not.     

Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are used as analgesic in postoperative pain to reduce opioid side effects, such as drowsiness and nausea. However, NSAIDs have not been used extensively in cardiac surgical patients due to the fear of untoward effects on gastric, renal, and coagulation parameters. This study will evaluate the efficacy and safety of three NSAIDs for pain control in CABG patients. METHODS: One hundred and twenty patients scheduled for elective CABG surgery were enrolled in randomized, double blind, controlled study. Standardized fast track cardiac anesthesia was used. One dose of drug (75 mg diclofenac, 100 mg ketoprofen, 100 mg indomethacin, or placebo) was given pr one hour before tracheal extubation and a second dose 12 hr later. Pain was treated with morphine iv and acetaminophen po. Visual analogue pain scores were recorded at baseline, 3, 6, 12 and 24 hr after the first dose of drug. RESULTS: There were no differences among the groups in pain scores. Only patients who received diclofenac required less morphine than patients in the control group (P < 0.05). When the total amounts of pain medications were computed to morphine equivalents, only patients in the diclofenac group received less pain medications than the placebo group (P < 0.05). Proportion of patients with postoperative increase of creatinine level (20% and over) did not differ between placebo and drug groups. CONCLUSION: Non-steroidal anti-inflammatory drugs may be used for analgesia management post CABG surgery in selected patients. Diclofenac appears to have the best analgesic effects by reducing the morphine and other analgesic requirement postoperatively.     

Ventilatory effects of a propofol infusion using a method to rapidly achieve steady-state equilibrium

The ventilatory effects of a propofol infusion were studied in 10 females premedicated with atropine and nine with papaveretum and atropine. The infusion, at a rate of 20 mg kg-1 h-1 for 5 min, reducing to 12 mg kg-1 h-1 for 10 min and then 6 mg kg-1 h-1 thereafter, was known to produce a steady-state plasma propofol concentration for 20-25 min after 25 min from commencement. Minute ventilation, tidal volume, frequency and response to breathing carbon dioxide were measured before the infusion and during the steady-state period. Propofol decreased minute ventilation to 56% and 46% (P less than 0.01) of their mean control values in the atropine and papaveretum groups, respectively. Mean tidal volume was decreased to 41-44% (P less than 0.02) by propofol, but a tachypnoea observed in the atropine group during the infusion was absent in the papaveretum group. Propofol alone had no effect on the slopes of the carbon dioxide response curves but did produce a shift to the right (P less than 0.05). Following papaveretum premedication the minute ventilation-carbon dioxide response curve slope, was decreased to 55% of its mean control volume value by the infusion, but this failed to reach statistical significance.     

The effect of diclofenac sodium ophthalmic solution on intraocular pressure following cataract extraction.

Ninety-two nonglaucomatous patients undergoing extracapsular cataract extraction with implantation of a posterior chamber intraocular lens by residents at a Veterans hospital were randomized in double-masked fashion to receive either a topical nonsteroidal antiinflammatory agent, diclofenac sodium 0.1%, or a placebo consisting of vehicle only. One drop of placebo or diclofenac sodium 0.1% was administered on an inpatient basis by trained staff every 6 hours for three doses, starting the afternoon prior to surgery. A further drop was given at 90, 60, 30, and 15 minutes before the operation. Starting 24 hours after surgery, all patients received diclofenac sodium 0.1%. All patients remained hospitalized for 72 hours postoperatively. Mean baseline intraocular pressure (IOP) was 14.0 and 14.1 mm Hg in the diclofenac and placebo groups, respectively. IOP rose 8.6 mm Hg in both groups at 6 hours after surgery. At 24 hours, the mean IOP elevation from baseline was 11.3 mm Hg in the diclofenac group and 9.6 mm Hg in the placebo group (P = .47). Within the first 24 hours, IOP spiked more than 10 mm Hg in 57% (26/46) of the diclofenac patients and in 54% (25/46) of the placebo patients. These results suggest that diclofenac sodium 0.1% drops affect neither the incidence nor the height of IOP elevation following cataract surgery.     

When do patients given intrathecal morphine need postoperative systemic opiates?

A prospective, randomised study has compared the requirements for intramuscular papaveretum after cholecystectomy in patients given either 0.8 mg intrathecal morphine preoperatively or intravenous papaveretum peroperatively. Patients given intrathecal morphine required significantly less papaveretum during the first 48 hours after operation, but no significant difference in analgesic requirements was observed by 72 hours due to a continuing demand for papaveretum by these patients.     

Intravenous diclofenac sodium decreases prostaglandin synthesis and postoperative symptoms after general anaesthesia in outpatients undergoing dental surgery

One hundred unpremedicated patients scheduled for outpatient restorative dentistry and/or oral surgery were given either 75 mg diclofenac sodium (prostaglandin synthesis inhibitor) or a saline placebo i.v. in a double-blind random fashion before induction of anaesthesia with methohexitone (2 mg/kg). Intubation was facilitated with suxamethonium (1.2 mg/kg) and anaesthesia was maintained with isoflurane in 50% nitrous oxide and oxygen using spontaneous respiration. Cuff pressure was continuously monitored and maintained at 10-25 mmHg. The mean duration of anaesthesia was 141 +/- 75 min in the diclofenac group and 150 +/- 73 min in the saline group. Diclofenac inhibited prostaglandin synthesis, as evident from serum thromboxane B2 and urinary 6-keto-prostaglandin F1 alpha data. There was no difference in recovery as assessed from the orientation time (14.2 +/- 5.7 min and 14.5 +/- 6.3 min for diclofenac and saline patients, respectively), perceptual speed and ability to walk along a straight line 30 and 60 min after anaesthesia. Emetic symptoms were equally common in both groups: an overall incidence of 32.6% and 36.7% for the diclofenac and saline patients, respectively. In the whole patient series women became nauseated and vomited more than men (P less than 0.01). Diclofenac reduced the incidence of pain in the throat or oral region 1 h after anaesthesia (P less than 0.05) and other symptoms 1-24 h postoperatively (P less than 0.01). Thus, preoperative intravenous diclofenac appears useful in ambulatory patients undergoing restorative dentistry and oral surgery under isoflurane anaesthesia.     

Effects of peri-operatively administered diclofenac and indomethacin on blood loss, bleeding time and plasma prostanoids in man

Sixty-seven patients scheduled for gynaecological laparotomy were anaesthetized with enflurane and divided at random into three groups to investigate double blind the effects of diclofenac (21 pts), indomethacin (23 pts) and placebo (23 pts) on haemostasis. Of each group eight to ten patients were chosen at random for estimation of peri-operative concentrations of prostanoids in plasma (thromboxane B2, prostaglandin E2). The pre-operative loading dose was diclofenac 33.6 mg or indomethacin 25 mg, followed by infusion for 24 h of diclofenac 6.7 mg h-1 or indomethacin 5 mg h-1. A fourth group received balanced anaesthesia (21 pts) and served as an additional control group for estimation of bleeding tendency and blood loss. The groups matched statistically for duration of surgery, age, weight, and height. No significant differences were found for prostaglandin E2 values, operation time, intra-operative blood loss, bleeding time, and frequency of post-operative haematomas. The most frequent surgeons' complaint was of increased bleeding tendency with indomethacin (P less than 0.001). Thromboxane B2 values in plasma were increased 30 min (66%) and 24 h (30%) after beginning of surgery in the placebo group (P less than 0.025). Diclofenac and indomethacin totally abolished these increases. During infusion of the loading dose of indomethacin one patient developed bradyarrhythmia, which was easily treated. No other complications appeared.