Methylprednisolone reduces pain, emesis, and fatigue after breast augmentation surgery: a single-dose, randomized, parallel-group study with methylprednisolone 125 mg, parecoxib 40 mg, and placebo

We compared methylprednisolone 125 mg IV (n = 68) and parecoxib 40 mg IV (n = 68) with placebo (n = 68) given before breast augmentation surgery in a randomized, double-blind parallel group study. Surgery was performed under local anesthesia combined with propofol/fentanyl sedation. Methylprednisolone and parecoxib decreased pain at rest and dynamic pain intensity from 1 to 6 h after surgery compared with placebo (mean summed pain intensity(1-6 h): methylprednisolone [17.25; 95% confidence interval [CI], 14.85-19.65] versus placebo [21.7; 95% CI, 19.3-24.1]; P < 0.03; parecoxib [15.25; 95% CI, 13.25-17.25] versus placebo; P < 0.001; mean summed dynamic pain intensity(1-6 h): methylprednisolone [22.7; 95% CI, 20.1-23.3] versus placebo [28.4; 95% CI, 26.0-30.8]; P < 0.01; parecoxib [20.9; 95% CI, 18.6-23.2] versus placebo; P < 0.001). Both rescue drug consumption and actual pain (all observations before and after rescue) during the first 6 h were similar in the two active drug groups and significantly reduced compared with placebo. Using a composite score of actual pain intensity and rescue analgesic use, the active drugs were significantly superior to placebo (P < 0.001 for both active drugs). Postoperative nausea and vomiting was reduced after methylprednisolone administration (incidence, 30%), but not after parecoxib (incidence, 37%), during the first 24 h compared with placebo (incidence, 60%; P < 0.001). Fatigue was reduced by methylprednisolone (incidence, 44%), but not by parecoxib (incidence, 59%), compared with placebo (incidence, 66%; P < 0.05). In conclusion, methylprednisolone 125 mg IV given before breast augmentation surgery had analgesic and rescue analgesic-sparing effects comparable with those of parecoxib 40 mg IV. Methylprednisolone, but not parecoxib, reduced nausea, vomiting, and fatigue.     

Methylprednisolone and ketorolac rapidly reduce hyperalgesia around a skin burn injury and increase pressure pain thresholds

BACKGROUND: Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) decrease acute postoperative pain and hyperalgesia. The objectives of this study were to investigate the effects of methylprednisolone and ketorolac on hyperalgesia around a skin burn injury and on pressure pain thresholds. METHODS: In a double-blind, placebo-controlled, randomized trial with cross-over design, methylprednisolone 125 mg, ketorolac 60 mg or placebo was administered intravenously in 12 male volunteers on three separate days at least 4 days apart. Primary and secondary hyperalgesia were produced by a first-degree burn injury on abdominal skin 45 min before injection of the test medicines. The area of secondary mechanical hyperalgesia outside the site of injury was measured. Pressure pain stimuli were applied on the base of a fingernail, increasing until the pressure pain detection threshold (PPDT) and pressure pain tolerance threshold (PPTT) were reached. RESULTS: Compared with placebo, the active drugs reduced the area of secondary hyperalgesia (methylprednisolone, P < 0.001; ketorolac, P < 0.01). Ketorolac but not methylprednisolone increased PPDT compared with placebo (P < 0.05). Both active drugs increased PPTT compared with placebo (methylprednisolone, P < 0.01; ketorolac, P < 0.001). Ketorolac increased PPTT more than methylprednisolone (P < 0.05). CONCLUSIONS: Methylprednisolone and ketorolac increased PPTT attenuated secondary hyperalgesia around a skin burn injury. PPTT increased after both methylprednisolone and ketorolac. The present study demonstrates analgesic and anti-hyperalgesic properties of a glucocorticoid and a non-selective NSAID that have not been demonstrated previously in human subjects.     

Preoperative ketorolac administration has no preemptive analgesic effect for minor orthopaedic surgery

The utility of preoperative ketorolac administration to reduce the intensity and duration of postoperative pain was compared with placebo in a randomized double-blind design of 60 ASA 1–2 patients scheduled for minor orthopaedic surgery. No opioids nor local anaesthetic blocks were used during surgery. The patients received either 30 mg ketorolac IV before surgery followed by a placebo injection after surgery or the reverse. Postoperative pain intensity was assessed repeatedly for 6 h using a visual analogue scale. No differences in pain intensity were observed between the two groups except for the initial 15-min postoperative assesments in the ketorolac group. The time to first rescue morphine administration and the total morphine consumption during the 6-h observation period were similar. It is concluded that the preoperative administration of ketorolac did not provide a significant preemptive analgesic benefit with regard to postoperative pain relief and opioid dose-sparing effect.     

Analgesic efficacy and safety of preoperative versus postoperative ketorolac in paediatric tonsillectomy

Background : Tonsillectomy is a common procedure in childhood resulting in significant morbidity due to pain. The aim of this study was to evaluate the analgesic efficacy and safety of a single dose of ketorolac i.v. given before or after tonsillectomy, compared to placebo.
Methods : A randomized, double-blind, placebo-controlled study was performed in 60 children, 5 to 15 years of age, admitted for tonsillectomy Patients were allocated to receive ketorolac 1 mg . kg^-1 i.v. or placebo. Postoperative pain was assessed by self-report 1.5, 3, 5, and 24 h after surgery.
Results : Pain scores were significantly lower for both ketorolac groups compared to the placebo group 1.5, 3, and 5 h after surgery ( P <0.05). Pain scores were lowest in the preoperative ketorolac group 1.5 to 5 h after surgery, and significantly fewer children in this group had fentanyl 0 to 1.5 h after surgery. But no significant differences were found between pain scores of the preoperative and postoperative ketorolac groups in the first 24 h after surgery. Acetaminophen consumption during the first 5 h after surgery was significantly less in patients receiving ketorolac ( P <0.05). Patients in the preoperative ketorolac group had a significantly lower incidence of postoperative vomiting ( P <0.05). There were no significant differences in the incidence of postoperative bleeding between groups. Three children in the preoperative, 5 children in the postoperative ketorolac group, and 5 children in the placebo group experienced postoperative haemorrhage.
Conclusion : This study indicates that a single dose of ketorolac 1 mg . kg^-1 i.v. administered either before or immediately after surgery improves postoperative analgesia in children after tonsillectomy without evidence of increased incidence of bleeding.     

KETOROLAC TROMETAMOL FOR POSTOPERATIVE ANALGESIA AFTER ORTHOPAEDIC SURGERY

We have compared the postoperative morphine requirements andanalgesic efficacy of four doses of i.m. ketorolac 30 mg administered6-hourly with placebo in a double-blind study of patients undergoingmajor or minor orthopaedic surgery. During the 24-h postoperativestudy period which began at the end of surgery, patients wereprescribed i.m. morphine 10 mg as required 2-hourly and assessmentswere made of pain at 4 and 24 h. After major surgery, the medianmorphine consumption over 24 h was 10 mg in patients who receivedketorolac, compared with 30 mg in those who received placebo(P = 0.008). Visual analogue pain scores and verbal pain assessmentswere better than placebo at 4 h (P = 0.028 and P = 0.008, respectively),but were not statistically different between the groups at 24h. Overall assessment of pain was similar in both groups whohad undergone major surgery. In the minor surgery groups, medianmorphine consumption was 0 mg in patients who received ketorolac,compared with 10 mg in those given placebo (ns). Visual analoguepain scores at 24 h after surgery were significantly less inpatients who had received ketorolac compared with placebo (P= 0.046) and the overall assessment of pain relief was betterin the ketorolac group (P = 0.0007). Mandatory administrationof ketorolac appeared to be of benefit in both major and minororthopaedic surgery, although the principal effects were reductionin requirement for supplementary morphine for major surgeryand better overall analgesia for minor surgery.     

A double-blind placebo-controlled comparison of a novel formulation of intravenous diclofenac and ketorolac for postoperative third molar extraction pain

Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N = 51 for all groups, except N = 47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P = .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia.     

Single-dose ketorolac and pethidine in acute postoperative pain: systematic review with meta-analysis

For a systematic review of postoperative analgesic efficacy and adverse effects of single doses, injected or oral, of pethidine and ketorolac compared with placebo, we sought published randomized studies in moderate to severe postoperative pain. Information on summed pain intensity or pain relief outcomes over 4-6 h was extracted and converted to dichotomous information to produce the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. Minor and major adverse effect data were extracted and summarized. For pethidine 100 mg i.m., eight randomized, controlled studies met the inclusion criteria, with 203 patients given pethidine and 161 placebo. The NNT to produce at least 50% pain relief was 2.9 (95% confidence interval 2.3-3.9). At this dose, pethidine produced significantly more drowsiness and dizziness than placebo, with numbers-needed-to-harm (NNH) of 2.9 (2.2-4.4) and 7.2 (4.8-14), respectively. For ketorolac, 14 reports met the inclusion criteria (six i.m. and eight oral). Most i.m. information (176 patients) was available for the 30 mg dose, which had an NNT of 3.4 (2.5-4.9). Most oral information was available for the 10 mg dose, which had an NNT of 2.6 (2.3-3.1). Oral ketorolac 10 mg was consistently at least as effective as ketorolac 30 mg i.m. Only with oral ketorolac 10 mg were there significantly more adverse effects than with placebo, with an NNH for any adverse effect of 7.3 (4.7-17).      

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

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

Improvement of pain treatment after major abdominal surgery by intravenous S+-ketamine

The use of intraoperative racemic ketamine for pain prevention after abdominal surgery is controversial. We compared one preincisional i.v. injection of S(+)-ketamine with its preincisional and repeated intraoperative use in 45 patients undergoing surgery with epidural and general anesthesia. S(+)-ketamine is a new drug formulation that contains the more potent S(+)-stereoisomer of ketamine. Patients were randomized to receive placebo, 0.5 mg/kg preincisional S(+)ketamine, or 0.5 mg/kg preincisional and 0.2 mg/kg intraoperative S(+)-ketamine repeated at 20-min intervals. In the postoperative period, epidural ropivacaine (2 mg/mL; 0.12 mL.kg(-1).h(-1)) was infused for pain therapy. Patients who received repeated S(+)-ketamine reported smaller pain scores than those who received placebo after awakening and 3 and 6 h later (P < or = 0.05). Fewer patients with repeated S(+)-ketamine required additional analgesics than those with placebo (P < or = 0.05). Cumulative consumption of additional diclofenac and dextropropoxyphene at 24 h was less after single (P < 0.05) and repeated (P < 0.05) S(+)-ketamine versus placebo. After awakening, patients who received repeated S(+)-ketamine reported being in a better mood than those in the other groups (P < 0.05). No psychotomimetic side effects were noted. In conclusion, preincisional and repeated intraoperative small-dose S(+)-ketamine added to general and epidural anesthesia causes better postoperative pain relief than general and epidural anesthesia alone. IMPLICATIONS: After major visceral surgery, preincisional and repeated intraoperative small-dose S(+)-ketamine added to general and epidural anesthesia causes better postoperative pain relief than general and epidural anesthesia alone.     

Efficacy of preoperative oral rofecoxib in pain control for third molar surgery.

OBJECTIVE: The study compared the analgesic efficacy of preoperative 50 mg oral rofecoxib, 400 mg ibuprofen, and placebo in the control of postoperative pain after third molar surgery. STUDY DESIGN: This was a clinical randomized, double-blind, cross-over, placebo- and active-comparator-controlled study. The surgeries were randomized into 3 groups, in which patients were given a single dose of 50 mg rofecoxib, 400 mg ibuprofen, or placebo 30-60 minutes before the surgery. The patients were asked to quantify their pain intensity basing on a visual analog scale postoperatively. A rescue medication, 500 mg acetaminophen, was prescribed to the patients. The quantity and time of consumption of the rescue tablets were recorded by the patients. RESULTS: A total of 49 patients completed the study. Of the 98 lower third molar extractions 33 were with rofecoxib, 33 ibuprofen, and 32 placebo. The pain scores within the first 6 hours postoperatively in the rofecoxib group were significantly lower than the placebo ( P < .05). The ibuprofen group did not have significantly lower pain scores than the placebo group. Regarding the postoperative requirement of rescue medication, the rofecoxib group required significantly less rescue medication than both ibuprofen and placebo groups in the first twelve hours after the surgery. CONCLUSIONS: The preoperative oral intake of 50 mg rofecoxib provides a significantly better analgesic benefit than the placebo for postoperative pain relief in the first 6 hours after third molar surgery. This regimen also reduced the requirement of postoperative analgesic when compared with ibuprofen and placebo in the first 12 postoperative hours.     

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.      

I.v. diclofenac and ketorolac for pain after thoracoscopic surgery

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.      

Preemptive Analgesic Effects of Ketorolac in Ankle Fracture Surgery

Background: Preemptive analgesia has been difficult to show in human experiments. If ketorolac has preemptive effects, then there may be an advantage to administering it at the beginning of surgery despite the potential for increased blood loss.

Methods: The authors performed a randomized, double-blind, controlled trial of 48 patients scheduled for ankle fracture surgery in a county trauma hospital. Anesthesia management was standardized and included adequate opioid analgesia (5 [mu]g/kg fentanyl and 0.1 mg/kg morphine). Intravenous 30 mg ketorolac was administered to 23 patients before tourniquet inflation and to 25 patients after tourniquet inflation. Visual analog scale pain scores, morphine patient-controlled analgesia consumption, nausea-vomiting, and postoperative bleeding were measured.

Results: The 23 patients given ketorolac before tourniquet inflation had no increase in pain postoperatively compared with their preoperative baseline (P = 0.280). The 25 patients who received ketorolac minutes later after tourniquet inflation had significant increases in their postoperative pain compared with their preoperative baseline (P = 0.00116). This effect was short-lived, and by 6 h the pain score in this group was not significantly more than it was preoperatively. Intergroup comparison showed a lower visual analog scale score at 2 (P = 0.0203) and 4 h (P = 0.00549) in the preemptive group and lower nausea scores at hour 6 (P = 0.00704). There was no difference in patient-controlled analgesia consumption between groups.     

Predictive factors for residual equinovarus deformity following Ponseti treatment and percutaneous Achilles tenotomy for idiopathic clubfoot: A retrospective review of 50 cases followed for median 2 years

Background and purpose The degree of postoperative pain is usually moderate to severe following knee arthroplasty. We investigated the efficacy of local administration of analgesics into the operating area, both intraoperatively and postoperatively.

Methods 40 patients undergoing unicompartmental knee arthroplasty (UKA) were randomized into 2 groups in a double–blind study (ClinicalTrials.gov identifier: NCT00653926). In group A (active), 200 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 106 mL) were infiltrated intraoperatively into the soft tissue, while in group P (placebo), no injections were given. 21 hours postoperatively, 150 mg ropivacain, 30 mg ketorolac, and 0.1 mg epinephrine were injected intraarticularly via a catheter in group A, whereas patients in group P were injected with the same volume of saline (22 mL).

Results Median hospital stay was shorter in group A than in group P: 1 (1–6) days as opposed to 3 (1–6) days (p < 0.001). Postoperative pain in group A was statistically significantly lower at rest after 6 h and 27 h and on movement after 6, 12, 22, and 27 h. Morphine consumption was statistically significantly lower in group A for the first 48 h, resulting in a lower frequency of nausea, pruritus, and sedation. Postoperatively, there were improved functional scores (Oxford knee score and EQ–5D) in both groups relative to the corresponding preoperative values.

Interpretation Local injection of analgesics periarticularly at the end of the operation and intraarticularly at 21 h postoperatively provided excellent pain relief and earlier home discharge following UKA. There was a high degree of patient satisfaction in both groups after 6 months (Clinical Trials.gov: NCT 00653926).     

Ketorolac and indomethacin are equally efficacious for the relief of minor postoperative pain

Injectable ketorolac is an effective analgesic in ambulatory surgery patients. However, no studies have compared ketorolac with other NSAIDs in this setting. The analgesic efficacy of intramuscular ketorolac, rectal indomethacin and placebo was compared in healthy women undergoing gynaecological or breast surgery as outpatients. Ninety patients received 30 mg im ketorolac, 100 mg pr indomethacin or placebo in a prospective, randomized, double-blind manner. A standardized anaesthetic protocol was followed. Patients graded their pain on a 10 cm visual analogue scale in the recovery room, twice in the surgical day care unit and during the car ride home. The patients’ postoperative fentanyl requirements, time to recovery milestones, and side effects were recorded. The placebo group received more fentanyl in the PACU but did not achieve the same pain relief as either of the NSAID-treated group (ketorolac 44 ± 53 μg, indomethacin 39 ± 55 μg, placebo 87 ± 100 μg, P < 0.05). Patients who received an NSAID had less pain at 15 and 90 min (P < 0.05). The PACU stay was longer for the placebo group (ketorolac 50 ± 13 min, indomethacin 49 ± 12 min, placebo 62 ± 35 min, P < 0.05). Time to ambulation was also longer in the placebo group (ketorolac 117 ± 25 min, indomethacin 121 ± 49 min, placebo 140 ± 51 min, P < 0.05). However, no differences were observed between the two NSAIDS. Side effects were similar in all groups. We conclude that im ketorolac and pr indomethacin are equally effective analgesics in this group of patients.     

Postoperative Modulation of Central Nervous System Prostaglandin E2 by Cyclooxygenase Inhibitors after Vascular Surgery

Background: The clinical availability of injectable cyclooxygenase inhibitors allows examination of the importance of cyclooxygenase 1 and 2 after surgery. The authors hypothesize that spinal prostaglandin E2 increases with lower extremity vascular surgery and that spinal prostaglandin E2 decreases with intravenous postsurgical administration of either a mixed cyclooxygenase 1/2 inhibitor (ketorolac) or a cyclooxygenase 2 selective inhibitor (parecoxib).

Methods: Thirty patients undergoing elective lower extremity revascularization under continuous spinal anesthesia had cerebrospinal fluid obtained at baseline and then up to 6 h after the start of surgery. Four hours after surgical incision, patients were randomized to receive intravenous parecoxib 40 mg, ketorolac 30 mg, or preservative-free normal saline. Patients were administered intravenous fentanyl in the postanesthesia care unit and acetaminophen/oxycodone on the surgical ward to control pain.

Results: Cerebrospinal fluid prostaglandin E2 concentrations were increased during and after surgery. After surgery, intravenous parecoxib 40 mg rapidly decreased cerebrospinal fluid prostaglandin E2, and intravenous ketorolac 30 mg also reduced cerebrospinal fluid prostaglandin E2 compared with placebo, but not as much as parecoxib. Postanesthesia care unit pain scores were reduced in the two drug groups compared with placebo, and surgical ward pain scores were also decreased for both drug groups, especially with parecoxib. No patient receiving parecoxib required postoperative intravenous fentanyl. Acetaminophen/oxycodone consumption was reduced in both drug groups compared with placebo, more so with parecoxib.     

Comparison of ketorolac and morphine for postoperative pain after major surgery

This study was designed to determine the relative analgesic efficacy and safety of single intramuscular injections of ketorolac (10 mg or 30 mg) and morphine (10 mg) in patients of either sex with moderate to severe pain after major surgery. In a single-dose, randomised, double-blind study of parallel design, pain was assessed immediately before injection of test medication and at regular intervals for 8 h thereafter. One hundred and seventeen patients (109 undergoing cardiac surgery; 8 lung surgery) were randomized to one of the three treatment groups. Pain intensity was assessed using a 5-point verbal scale before administration of study drugs. Postadministration, at 30 min and hourly for 8 h, pain intensity and pain relief were assessed, again using the 5-point verbal scale. Additionally, as a measure of analgesia, forced expiratory volume (FEV1) was obtained in all patients. Vital signs including blood pressure, pulse, temperature, respiratory rate and blood gases (PaCO2) were recorded prior to and after study medication. Based on hourly pain intensity differences and hourly pain relief observations, ketorolac 10 mg was generally more effective than morphine 10 mg, and ketorolac 30 mg was generally more effective than ketorolac 10 mg. The results of this study show that ketorolac is an effective and safe (with regard to arterial pressure, blood gases and lung function) analgesic for relief of postoperative pain after major surgery in stable patients. No clinically significant adverse effects occurred during the study. One cannot exclude an influence on patients with organ system dysfunction or on parameters not measured in this study.     

Preemptive analgesic effects of ketorolac in ankle fracture surgery

BACKGROUND: Preemptive analgesia has been difficult to show in human experiments. If ketorolac has preemptive effects, then there may be an advantage to administering it at the beginning of surgery despite the potential for increased blood loss. METHODS: The authors performed a randomized, double-blind, controlled trial of 48 patients scheduled for ankle fracture surgery in a county trauma hospital. Anesthesia management was standardized and included adequate opioid analgesia (5 microg/kg fentanyl and 0.1 mg/kg morphine). Intravenous 30 mg ketorolac was administered to 23 patients before tourniquet inflation and to 25 patients after tourniquet inflation. Visual analog scale pain scores, morphine patient-controlled analgesia consumption, nausea-vomiting, and postoperative bleeding were measured. RESULTS: The 23 patients given ketorolac before tourniquet inflation had no increase in pain postoperatively compared with their preoperative baseline (P = 0.280). The 25 patients who received ketorolac minutes later after tourniquet inflation had significant increases in their postoperative pain compared with their preoperative baseline (P = 0.00116). This effect was short-lived, and by 6 h the pain score in this group was not significantly more than it was preoperatively. Intergroup comparison showed a lower visual analog scale score at 2 (P = 0.0203) and 4 h (P = 0.00549) in the preemptive group and lower nausea scores at hour 6 (P = 0.00704). There was no difference in patient-controlled analgesia consumption between groups. CONCLUSIONS: Intravenous 30 mg ketorolac appears to have preemptive analgesic effects in patients undergoing ankle fracture repair. Ketorolac administered before tourniquet inflation prevents postoperative pain being perceived as more intense than preoperative pain.     

Postoperative modulation of central nervous system prostaglandin E2 by cyclooxygenase inhibitors after vascular surgery

BACKGROUND: The clinical availability of injectable cyclooxygenase inhibitors allows examination of the importance of cyclooxygenase 1 and 2 after surgery. The authors hypothesize that spinal prostaglandin E2 increases with lower extremity vascular surgery and that spinal prostaglandin E2 decreases with intravenous postsurgical administration of either a mixed cyclooxygenase 1/2 inhibitor (ketorolac) or a cyclooxygenase 2 selective inhibitor (parecoxib). METHODS: Thirty patients undergoing elective lower extremity revascularization under continuous spinal anesthesia had cerebrospinal fluid obtained at baseline and then up to 6 h after the start of surgery. Four hours after surgical incision, patients were randomized to receive intravenous parecoxib 40 mg, ketorolac 30 mg, or preservative-free normal saline. Patients were administered intravenous fentanyl in the postanesthesia care unit and acetaminophen/oxycodone on the surgical ward to control pain. RESULTS: Cerebrospinal fluid prostaglandin E2 concentrations were increased during and after surgery. After surgery, intravenous parecoxib 40 mg rapidly decreased cerebrospinal fluid prostaglandin E2, and intravenous ketorolac 30 mg also reduced cerebrospinal fluid prostaglandin E2 compared with placebo, but not as much as parecoxib. Postanesthesia care unit pain scores were reduced in the two drug groups compared with placebo, and surgical ward pain scores were also decreased for both drug groups, especially with parecoxib. No patient receiving parecoxib required postoperative intravenous fentanyl. Acetaminophen/oxycodone consumption was reduced in both drug groups compared with placebo, more so with parecoxib. CONCLUSIONS: Cerebrospinal fluid prostaglandin E2 is elevated in patients after lower extremity vascular surgery. Postsurgical intravenous administration of the cyclooxygenase 1/2 inhibitor ketorolac, and especially the cyclooxygenase 2 inhibitor parecoxib, reduces cerebrospinal fluid prostaglandin E2 concentration and postoperative pain.     

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

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

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

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