Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery. Ketorolac is not nephrotoxic in connection with sevoflurane anesthesia in patients undergoing breast surgery. Effects of ketorolac trometamol on renal function. Tenoxicam i.v. for major gynaecological surgery--effects on renal function. Single dose parecoxib significantly improves ventilatory function in early extubation coronary artery bypass surgery: a prospective randomized double blind placebo controlled trial. Use of ketorolac after lower abdominal surgery. Effect on analgesic requirement and surgical outcome. Postoperative naproxen after coronary artery bypass surgery: a double-blind randomized controlled trial. Pain treatment with a COX-2 inhibitor after coronary artery bypass operation: a randomized trial. Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery. Effect of diclofenac on renal function and prostacyclin generation after surgery. Indomethacin as adjunct analgesia following open cholecystectomy. The effects of perioperative ketorolac infusion on postoperative pain and endocrine-metabolic response. Morphine-sparing effect of ketoprofen after abdominal surgery. Tenoxicam does not alter renal function during anaesthesia in normal individuals. Intravenous ketoprofen for pain relief after total hip or knee replacement. IV diclofenac in post-thoracotomy pain. [Does the preoperative administration of ketorolac improve postoperative analgesia]. Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain. A double-blind, placebo-controlled, multicenter study. Peri-operative administration of rectal diclofenac sodium. The effect on renal function in patients undergoing minor orthopaedic surgery. Prospective double-blind study of effect of ketorolac administration after laparoscopic urologic surgery. Ibuprofen does not impair renal function in patients undergoing infrarenal aortic surgery with epidural anaesthesia. I.v. diclofenac and ketorolac for pain after thoracoscopic surgery.
To evaluate the combination of rectal indomethacin with patient controlled intravenous morphine analgesia (PCA) on postoperative pain relief and opioid use after cardiac surgery.
                With institutional ethics approval, 57 consenting adults undergoing elective aortocoronary bypass surgery were randomly assigned preoperatively in a double-blind fashion to receive either placebo (n = 26) or indomethacin 100 mg suppositories (n = 31), 2-3 hr postoperatively, and 12 hr later. Both groups utilized PCA morphine. Pain scores in the two treatment groups were assessed on a 10-cm visual analogue scale (VAS) (at rest and with cough) at 4, 6, 12, 18 and 24 hr after initial dosing, and were analyzed through a 2 x 5 repeated measures of variance. The 24 hr analgesic consumption, 12 and 24 hr chest tube blood loss, and time to tracheal extubation were also recorded, and compared for the two treatment arms through Student's t test on independent samples.
                Postoperative morphine consumption in the first 24 hr was 38% less in the indomethacin group (22.40 +/- 12.55 mg) than the placebo group (35.99 +/- 25.84 mg), P = 0.019. Pain scores, measured with a VAS, were 26% to 66% lower in the indomethacin vs placebo group at rest (P = 0.006), but not with cough, for all times assessed. There was no difference in blood loss (at 12 hr) or time to tracheal extubation for both groups.
                The combination of indomethacin with morphine after cardiac surgery results in reduced postoperative pain scores and opioid use without an increase in side effects. Ketorolac, which may cause renal vasoconstriction by cyclooxygenase inhibition, is often administered to patients anesthetized with sevoflurane that is metabolized to inorganic fluoride (F(-)), another potential nephrotoxin. We assessed this possible interaction using urine N-acetyl-beta-D-glucosaminidase indexed to urinary creatinine (U-NAG/crea) as a marker of proximal tubular, beta2-microglobulin as a tubular, urine oxygen tension (P(u)O(2)) as a medullary, and erythropoietin as a marker of tubulointerstitial damage. Thirty women (ASA physical status I-II) undergoing breast surgery were included in our double-blinded study. They were allocated into two groups receiving either ketorolac 30 mg IM (Group K) or saline (Group C) at the time of premedication, at the end of, and 6 h after anesthesia maintained with sevoflurane. Urine output, U-NAG/crea, P(u)O(2,) serum creatinine, urea, and F(-) were assessed. Blood loss was larger in Group K (465 +/- 286 mL vs 240 +/- 149 mL, mean +/- SD, P < 0.05). The MAC-doses of sevoflurane were similar. U-NAG/crea increased during the first 2 h of anesthesia and serum F(-) peaked 2 h after the anesthesia without differences between the groups. There were no statistically significant changes in P(u)O(2), erythropoietin, beta2-microglobulin, serum creatinine, urea, or urine output during anesthesia or the recovery period in either group. Our results indicate that the kidneys are not affected by ketorolac administered in connection with sevoflurane anesthesia.
                The different kinetics of N-acetyl-beta-D-glucosaminidase indexed to urinary creatinine and serum inorganic fluoride during and after sevoflurane anesthesia suggest that the observed mild renal tubular function deterioration is not caused by inorganic fluoride. Administration of ketorolac IM is therefore considered safe in adequately hydrated healthy adult patients given sevoflurane anesthesia. We have compared the renal effects of ketorolac trometamol 10 mg administered 4-hourly by intermittent i.m. injection or by continuous i.m. infusion with placebo in a double-blind study in 67 patients who had undergone upper abdominal surgery. Ketorolac was supplemented during the 48-h postoperative study period with bolus doses of morphine delivered by a patient controlled analgesia system. The only significant effect of ketorolac on renal function compared with patients who received placebo was reduced excretion of potassium. The overall changes caused by surgery alone were of much greater magnitude. Bleeding time was increased with ketorolac, but there were no adverse events related to this. Thirty women presenting for major gynaecological oncology surgery under a standardized, combined epidural/general anaesthetic technique received either placebo or tenoxicam 20 mg intravenously, in a randomized double-blinded manner prior to surgery. Plasma and urinary electrolytes, creatinine, prostaglandins PgE2 and PgF1 alpha, and thromboxane (TxB2) were collected 12 hours preoperatively and then for four days postoperatively. There were no significant differences in any of the measured parameters between the groups, at any of the measurement times. Mean (SD) creatinine clearance at baseline, 24 h and 48 h was 100.4 (29.7) and 86.9 (27.5), 128.1 (45.9) and 115.0 (40.3), 137.5 (50.7) and 121.6 (38.6) in the placebo and tenoxicam groups respectively (P = 0.28). Both groups required similar amounts of intraoperative ephedrine and intravenous fluids to maintain blood pressure. The minimal changes in plasma and renal parameters reflect predictable responses to major surgery and rehydration rather than any response to cyclooxygenase inhibition. This may underscore the importance of maintenance of blood pressure during the course of surgery and postoperative care, and perhaps the usefulness of a fluid loading regimen to preserve renal function during surgery. The predicted attenuation of renal prostaglandin-mediated protective mechanisms and enhancement of the catecholamine-mediated renal vasoconstriction by the use of a single 20 mg dose of tenoxicam in this study were not seen. Modulation of renal concentrating mechanisms or excretion of sodium and potassium by tenoxicam was not apparent and a large increase in study size would be required to detect a significant difference in these parameters as a consequence of the drug, over and above any changes in response to surgery and epidural anaesthesia. Parecoxib, a cyclo oxygenase-2 inhibiting non-steroidal anti-inflammatory drug, has been widely used for postoperative analgesia. Our aim was to quantify the benefit of a single dose after coronary artery bypass grafting.
                The investigation was carried out as a randomized double blind placebo controlled study. A single i.v. dose of parecoxib 40 mg or placebo was given at closure of sternotomy. No opioid other than morphine was given in the first 24 postoperative hours. Pain was assessed using both a Visual Analogue Score (1-10), and the amount of morphine used via a morphine patient controlled analgesia pump. Creatinine clearance was measured before and after operation from 24 h urine collections. After a global announcement by Pfizer that paracoxib was 'contraindicated in patients with ischaemic heart disease' further recruitment was suspended and the collected data from 40 patients were analysed.
                Twenty-one patients received parecoxib and 19 received placebo. Amongst those who received parecoxib, there was a highly significant sparing of rescue medication before tracheal extubation (P=0.004) compared with placebo, and an overall 35% morphine sparing effect during the first 6 h post extubation after correction for the variability in extubation time (P=0.037). Respiration, as measured by arterial carbon dioxide tension at the time of extubation, was significantly better in the parecoxib group (P=0.045). Significantly more furosemide was given for postoperative oliguria in those patients who received parecoxib (P=0.036). After correcting for differences in diuretic usage and fluid balance, parecoxib was associated with a significant increase in plasma creatinine (P=0.041).
                A single dose of parecoxib has a significant opioid sparing effect in the first 6 h after coronary artery bypass grafting which resulted in significantly improved ventilation with mild elevation of plasma creatinine within normal limits. Ketorolac is a nonsteroidal antiinflammatory agent with opioid-sparing properties. The effect of ketorolac on postoperative opioid analgesic requirement and surgical outcome was evaluated in 198 women after abdominal hysterectomy procedures using a double-blind protocol design.
                Patients were randomly assigned to receive either 60 mg intravenous (2 ml) ketorolac, followed by 30 mg intravenously (in saline 20 ml) over 30 min every 6 h, or 2 ml intravenous saline, followed by saline 20 ml intravenously over 30 min every 6 h, for up to 72 h. The postoperative opioid analgesic requirement was assessed using a patient-controlled analgesia (PCA) device to self administer either morphine or meperidine. The authors also evaluated pain, sedation (or drowsiness), fatigue, quality of sleep, and postoperative side effects at 2-8-h intervals for up to 72 h after surgery.
                Ketorolac decreased the PCA opioid usage on the night of operation and during the first postoperative day. Ketorolac also improved the quality of sleep during the first night after surgery. Although ketorolac- (vs. saline-) treated patients had a significantly shorter time to passage of bowel gas (50 +/- 24 h vs. 61 +/- 25 h), there were no clinically significant differences in the times to oral intake, unassisted ambulation, or hospital discharge. There were also no differences in the overall incidence of side effects in the ketorolac- (vs. saline-) treated patients. However, the use of ketorolac with opioid PCA was associated with a reduced need for antiemetic therapy on the postsurgical ward.
                The authors conclude that the opioid-sparing effects of ketorolac contributed few clinically significant advantages after abdominal hysterectomy procedures. Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used after coronary artery bypass surgery (CABG), yet their effects have seldom been evaluated in randomized controlled settings. The aim of this study was to examine the efficacy and safety of a commonly used NSAID, naproxen. We hypothesized that naproxen would reduce postoperative pain following CABG without increasing complications.
                Patients (N=98) undergoing primary CABG were randomized to receive naproxen (500 mg q12hX5 doses via suppository started 1h after operation, followed by oral 250 mg q8hX6 doses) or placebo. Standard analgesic and anti-emetic regimens were available to both patient groups. Interventions were double-blinded. Primary end-points were postoperative pain measured before and after chest physiotherapy by visual analog scale and pulmonary slow vital capacity (SVC).
                Baseline characteristics were equivalent between the two groups. Over the first 4 postoperative days, naproxen decreased pain by 47+/-17% on average before chest physiotherapy (P=0.034), and 44+/-13% after chest physiotherapy (P=0.0092). Patients who received naproxen also had better preservation of SVC over the first 4 postoperative days (mean loss of SVC from baseline: 2.1+/-0.1 vs. 2.5+/-0.1l, naproxen vs. placebo, P=0.0032). This was concomitant with a lower white blood cell count observed in naproxen patients (9.2+/-0.3 vs. 12.7+/-1.5x10(9)/l, naproxen vs. placebo, P=0.03). Patients who received naproxen had more chest tube drainage after 4h postoperatively, but there was no difference in the incidence or amount of transfusions. There was no difference in medication use, length of stay, or in the incidence of atrial fibrillation, azotemia, and other complications.
                Naproxen is an effective and low-cost adjunct for optimization of pain control and lung recovery after CABG. Its use may result in increased chest tube drainage, but no apparent increase in other complications. Adequate analgesic medication is mandatory after cardiac operations. Cyclooxygenase-2 inhibitors represent a new therapeutic option, acting primarily on the response to inflammation.
                We compared a cyclooxygenase-2 inhibitor (etodolac) with two traditional drugs: a nonselective cyclooxygenase inhibitor (diclofenac) and a weak opioid (tramadol) on postoperative pain and renal function in patients undergoing coronary artery bypass operations. Sixty consecutive patients were randomized into three groups: (1) group A patients who received tramadol; (2) group B patients who received diclofenac; and (3) group C patients who received etodolac. For measurement of analgesic effect, the visual analogue scale was assessed up to postoperative day 4. Creatinine-clearance was determined before and at the end of study medication, and serum creatinine and urea were monitored daily for renal effects. Study medication was given on postoperative days 2 and 3. Side effects and additional pain medication were recorded.
                The visual analogue scale was lower in group C (p < 0.05) from postoperative days 2 to 4 and in group B (p < 0.05) from postoperative days 3 to 4 compared with group A. Amount of additional pain medication and incidence of side effects were significantly less in group C compared with group A. We observed a short-lasting elevation of serum creatinine and urea in groups B and C compared with group A (p < 0.05).
                At the doses analyzed, etodolac and diclofenac produced better postoperative pain relief with less side-effects than tramadol. A short-lasting impairment of renal function was found in patients treated with etodolac and diclofenac. 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.
                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.
                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.
                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. We have examined the effect of diclofenac on renal function after major surgery in a randomized, double-blind, controlled study of 20 patients undergoing oesophagogastrectomy. Diclofenac 75 mg or placebo was given i.m. 12-hourly for 2 days. I.v. fluid administration was standardized. Renal function was assessed by fluid balance and measurement of serum creatinine and electrolyte concentrations, creatinine and free water clearance, and urinary sodium and potassium excretion. Urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) was measured by radioimmunoassay to assess renal prostacyclin production. After surgery, 6-keto-PGF1 alpha production increased, but this did not occur with diclofenac. On the first day after surgery, use of diclofenac was associated with a decreased urine flow rate, decreased urinary sodium and potassium excretion and a tendency to hyperkalaemia. Frusemide was required more often in the diclofenac group. One patient was withdrawn from the diclofenac group because of impaired renal function. Urine flow rate and blood potassium concentration should be monitored if diclofenac is used after major surgery. Fifty patients scheduled for elective cholecystectomy were randomised to receive either indomethacin suppositories 200 mg p.r. at the end of anaesthesia, followed by 100 mg bd for three days, or placebo suppositories according to the same regimen. All patients were given intravenous pethidine via patient-controlled analgesia (PCA) postoperatively. The mean dose of pethidine required by the patients in the indomethacin group was significantly less than that used by the placebo group, the cumulative dose after three days being 530.7 mg (SD 664.0) and 1151.0 mg (682.0) for the indomethacin and placebo groups respectively. At the same time the patients in the indomethacin group had lower pain scores both at rest and with movement, though this was only statistically significant on the first day on movement. There was no statistical difference between the groups with respect to the incidence of nausea, indigestion, proctitis, volume of drainage from the wound drain, or width of bruising around the wounds. Serum creatinine levels were compared pre- and postoperatively where possible and showed no change in either group. We designed a randomized, double-blind study to assess the analgesic efficacy and safety of perioperative ketorolac infusion in 95 patients undergoing cholecystectomy. The ketorolac group (n = 48) received premedication, combined with ketorolac 30 mg intramuscularly (IM), followed by a ketorolac continuous infusion (2 mg/h). The control group (n = 47) received an IM bolus of NaCl 0.9% (1 mL) followed by continuous saline infusion (2 mL/h) for 24 h. Operative blood losses, postoperative pain, sedation, and on-demand morphine consumption (patient-controlled analgesia [PCA]) were measured. The effects on plasma catecholamines, cortisol, potassium, creatinine, skin bleeding time, prothrombin time (PT), and partial thromboplastin time (PTT) were also evaluated. Ketorolac improved pain scores (P < 0.05) and reduced plasma cortisol concentrations between 2 and 6 h (P < 0.05). No significant differences were observed concerning operative blood losses, glucose concentration, and renal and hemostatic functions. The ketorolac group required less morphine (not significant [NS]) than the control group and had less adverse effects (P = 0.002). Thus, perioperative ketorolac infusion improved the quality of postoperative pain relief, and had no major influence on endocrine-metabolic response and no negative influences on hemostatic and renal functions. This study suggests that preventive ketorolac administration, followed by a continuous infusion, is an easy, useful, and safe method for pain control after abdominal surgery. In a double-blind, placebo-controlled clinical trial (power of 80% to detect a 30% reduction in morphine consumption, P < 0.05), we have determined that the administration of two doses of intravenous ketoprofen 100 mg, one at the end of surgery and the second 12 hours postoperatively, was associated with a significant reduction in morphine consumption at eight (P = 0.028), 12 (P = 0.013) and 24 hours (P = 0.013) but not four hours (P = 0.065) postoperatively, as compared to placebo, when assessed by patient-controlled analgesia. There was no difference between the groups in pain scores or in the incidence of nausea and vomiting. One patient in the placebo group suffered from excessive sedation while one patient from the ketoprofen group suffered from transient oliguric renal failure. There were no other adverse effects. The results of this study show that ketoprofen does provide a morphine-sparing effect in the management of postoperative pain after abdominal surgery. Anaesthesia and surgery alter renal function. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs (NSAIDs) administered with anaesthesia may further compromise renal function.
                To study the effects of tenoxicam (NSAID) administered immediately prior to anaesthesia on renal function in normal individuals undergoing routine surgery.
                A randomised single blind placebo controlled study comparing tenoxicam (40 mg intravenously) with placebo was carried out in 20 healthy (ASA I) patients undergoing lower spinal surgery. Glomerular filtration rate (GFR) was determined by creatinine clearance and renal tubular function measured as osmolar and free water clearance.
                GFR fell by 60% at the end of surgery but returned to pre-operative values by six hours post-operatively. There was no difference between placebo or tenoxicam with regard to changes in GFR. Tubular function was not altered by tenoxicam.
                Current clinical practice of using NSAIDs for post-operative analgesia in low risk individuals appears to have no adverse effects on renal function. There are few studies in which ketoprofen, a propionic acid derivate NSAID, has been tested as an intravenous postoperative analgesic. The aim of this double-blind, randomized, placebo-controlled work was to study the tolerability and efficacy of intravenous ketoprofen in seventy-six patients undergoing hip or knee total endoprothesis surgery using three different doses.
                The patients received either ketoprofen 50 mg, 100 mg or 150 mg, or placebo as an initial intravenous loading, followed by an infusion containing 50 mg, 100 mg or 150 mg or placebo, respectively, over the following eleven and a half hours. The consumption of fentanyl was recorded and the patients assessed their pain intensity on a 10-cm visual analogue scale (VAS) at 0, 2, 4 and 12 hours. Possible side-effects were recorded at the same intervals.
                Patients receiving ketoprofen showed significantly lower total fentanyl consumption and significantly better pain relief at 12 hours was achieved by a 300 mg dose of ketoprofen than by placebo. Side-effects were minimal, with no differences between the groups.
                A bolus of ketoprofen following continuous infusion of ketoprofen, coupled with a PCA-system, was an effective and safe approach for the relief of postoperative pain. We have studied the efficacy of a continuous i.v. infusion of diclofenac 2 mg kg-1/24 h given for 2 days after major thoracic surgery in 30 patients in a double-blind, placebo-controlled, parallel-group design. The patients were able to obtain additional pain relief as on demand morphine boluses. In the diclofenac group, the consumption of morphine was reduced by 60% during the first and by 76% during the second day after operation compared with the control group. Overall, analgesia was also superior in the diclofenac group. Arterial oxygenation was significantly greater and the arterial PCO2 increased less during the first day after operation in the diclofenac group compared with the control group. Diclofenac had no significant effect compared with placebo on blood loss or on any bleeding or platelet test. Urine output was significantly less during the first day after operation in the diclofenac group compared with the control group, but was normal on the second day after operation; plasma creatinine concentrations were unchanged. I.v. diclofenac infusion combined with opioids delivered via a patient-controlled analgesia device seems a valuable method of pain relief after thoracic surgery in patients in whom more invasive techniques, such as extradural local anaesthetics and opioids, cannot be used. However, non-steroidal anti-inflammatory drugs should be used cautiously, if at all, in patients who are at risk of acute renal failure. 1) To verify the usefulness of ketorolac administration (30 mg i.v.) before a surgical operation in terms of postoperative analgesia improvement; 2) To evaluate the impact of preoperative ketorolac administration on perioperative renal function and on intraoperative water balance; 3) to evaluate the presence of adverse effect due to preoperative NSAID use.
                Prospective randomized trial.
                University surgical department.
                Forty adult patients undergoing major abdominal surgery, randomized in 2 groups: in group 1 ketorolac (30 mg i.v.) was administered immediately after the induction and, for postoperative analgesia, ketorolac (30 mg i.v.) was administered beginning at the time of skin closure; in group 2 no ketorolac was administered before the operation and postoperative treatment was the same. Buprenorphine (0.3 mg i.m.) was administered in case of unsatisfactory analgesia. Fluids infused and diuresis were measured intraoperatively. One, 6 and 24 hours after the end of operation pain was evaluated using pain intensity score and VAS. The day after the operation serum creatinine and urea were measured.
                No statistically significant differences were found between groups regarding fluids infused, intraoperative diuresis, postoperative pain, adverse effects and number of bleeding episodes. More than 50% of patients, in either groups, required opioids administration.
                Ketorolac (30 mg i.v.) administration before a major abdominal operation does not improve postoperative analgesia nor determines significant alterations in renal function or increase in the frequency of abnormal bleedings. Opiate administration is necessary in more than 50% of the patients to achieve adequate analgesia. Ketorolac is a nonsteroidal analgesic that may provide postoperative analgesia without opioid-related side effects. This double-blind, randomized, multicenter study evaluated the analgesic efficacy and safety of intravenous ketorolac in 207 patients during the first 24 h after major surgery.
                Subjects were assigned to receive one of three analgesic regimens: a ketorolac infusion, ketorolac boluses, or placebo. All subjects had access to intravenous morphine via patient-controlled analgesia (PCA). Evaluations included PCA morphine used, pain assessment (categorical pain intensity scores and visual analogue pain scores), pain relief (categorical pain relief scores), sedation, presence of adverse events, and overall rating of regimens by study observers and patients.
                Patients in the ketorolac infusion group (but not the ketorolac bolus group) used less morphine (average 33 mg) than did the placebo group (44 mg) (P = 0.009). Significant differences favoring both ketorolac groups were seen in the pain intensity and the categorical pain relief scores at various time points during the study. At the termination of the study, compared with the placebo group, categorical pain intensity scores were lower in the ketorolac bolus group; visual analogue pain scores were lower in both ketorolac groups; and pain relief scores were higher in the ketorolac bolus group. The incidence of vomiting was significantly greater in the placebo group (27%) than in the ketorolac infusion group (12%) or bolus group (9%) (P = 0.032 and P = 0.005, respectively). The incidence of postoperative fever was 10% in the ketorolac bolus group and 25% in the placebo group (P = 0.013). Study observers noted less nursing difficulty while caring for patients in the ketorolac infusion group (P = 0.015). Study observers and patients in both ketorolac groups reported statistically significant overall drug superiority compared with placebo.
                It is concluded that intravenous boluses or infusions of ketorolac in conjunction with PCA morphine provide effective, safe analgesia after major surgery and improve on the response to PCA morphine alone. In a randomized, double-blind study, we administered placebo and diclofenac sodium 100 mg suppositories 1 h pre-operatively and on the first post-operative morning to 22 adult patients undergoing minor orthopaedic surgery. A standardized post-operative intravenous fluid regimen was instituted until oral fluids were tolerated. Renal function was assessed pre-operatively, and on the first and second post-operative days by the measurement of urine output, creatinine, urea, sodium, potassium and NAG (N-acetyl-b-D-glucosaminidase) levels and serum creatinine, urea, sodium and potassium concentrations. On the first post-operative day, the diclofenac group demonstrated a reduced urinary sodium excretion. On the second post-operative day, a reduced urinary NAG/creatinine ratio was observed in the diclofenac group when compared to placebo. We conclude that peri-operative administration of diclofenac causes changes in renal function consistent with prostaglandin inhibition on the first post-operative day but had no lasting adverse effects in this group of patients. Our results reinforce the need for caution when administering this drug in the context of pre-existing renal impairment. To decrease postoperative dependence on narcotics for analgesia, we have evaluated ketorolac as an adjunct to perioperative pain control in patients undergoing laparoscopic urologic surgery.
                Sixty-five patients (34 male, 31 female) were randomized to receive either ketorolac tromethamine (15-30 mg IV q 6 h) or placebo prior to laparoscopic surgery. Patient-controlled analgesia in the form of morphine sulfate was provided. Operative factors such as the type of surgery, operative time, and estimated blood loss were recorded. Postoperative factors such as analog pain score (range 0-10), narcotic usage, and length of stay were evaluated.
                Fifty-five patients completed the study. The average pain score was 2.2 and 4.5 for the ketorolac and placebo groups, respectively (P < 0.005). The mean amounts of total morphine used were 39.2 mg (ketorolac) and 62.5 mg (placebo) (P = 0.077). The length of stay was not significantly different in the ketorolac (2.5 days) and placebo (2.6 days) groups (P = 0.74). Operative times (P = 0.21) and estimated blood loss (P = 0.60) were not significantly different in the two groups. Ketorolac did not adversely affect renal function; serum creatinine changes were not significantly different from those in the patients receiving placebo (P = 0.50). Laparoscopic pyeloplasty necessitated more narcotic analgesia than did other laparoscopic procedures (P = 0.05).
                Ketorolac decreases the subjective perception of pain after laparoscopic urologic surgery. It is suggested that ketorolac administration decreases the amount of narcotic usage as well. Time to resumption of oral intake and length of hospital stay were not influenced by use of ketorolac. To investigate the effect of preoperative ibuprofen administration on renal function during and after infrarenal aortic surgery under thoracolumbar epidural anaesthesia (EPA).
                A prospective randomised, double-blinded clinical study.
                Operation room and intensive care unit in a university hospital.
                Twenty-six consecutive patients scheduled for elective infrarenal aortic surgery.
                The patients were prospectively randomised to receive 400 mg ibuprofen intravenously (i.v.) or a placebo aliquot before surgery.
                We assessed renal function by calculating creatinine clearance, and fractional sodium excretion before surgery (baseline), 1 h after cross-clamping (intraoperative), 6 h after cross-clamping (postoperative) and 24 h after cross-clamping (on the 1 st postoperative day). At each point in time, we additionally registered haemodynamics and determined the plasma concentration of 6-keto-PGF1alpha (stable metabolite of prostacyclin, PGI2), bicyclic PGE2 (stable metabolite of PGE1 E2), active renin, aldosterone and vasopressin by radioimmunoassays. Throughout the observation period the renal function parameters mostly remained within the normal range without a significant difference between ibuprofen- and placebo-treated patients (creatinine clearance: baseline 41 +/- 3 vs 38 +/- 6, intraoperative 57 +/- 8 vs 64 +/- 11, postoperative 64 +/- 9 vs 56 +/- 9, first postoperative day 43 +/- 5 vs 47 +/- 6 ml x min x m(-2), means +/- SEM). The plasma levels of 6-keto-PGF1alpha (68 +/- 8 vs 380 +/- 71* ng x l(-1)), bicyclic PGE2 (57 +/- 5 vs 88 +/- 9* ng x l(-1)) and vasopressin (14 +/- 7 vs 45 +/- 10* ng x l(-1), p < 0.0125), however, were significantly higher during the intraoperative period in the placebo-treated patients.
                The inhibition of endogenous prostaglandin release by ibuprofen does not substantially impair renal function during infrarenal aortic surgery under EPA. We studied intensity of pain, cumulative morphine consumption, ventilatory and renal function, and haemostasis in patients undergoing video-assisted thoracoscopic surgery and receiving a 2-day i.v. infusion of diclofenac, ketorolac or saline. Plasma concentrations of the two NSAID were also measured. The study was randomized, double-blind and placebo-controlled, with 10 patients in each group. Patients experienced mainly moderate pain. Mean consumption of i.v. morphine during the first day after operation was 57 (SEM 11) mg in the placebo group. Diclofenac and ketorolac were equally effective in reducing total morphine consumption (61% and 52%, respectively). Adverse events were similar and minor. Greater variability in plasma concentrations of ketorolac were detected compared with diclofenac.
NSAIDs caused a clinically unimportant transient reduction in renal function in the early postoperative period in patients with normal preoperative renal function. NSAIDs should not be withheld from adults with normal preoperative renal function because of concerns about postoperative renal impairment.