ABSTRACT
BACKGROUND: Non-steroidal anti-inflammatory drugs are often used as part of multimodal analgesia to control postoperative pain. This randomized, controlled, double-blinded, non-inferiority study aimed to compare the postoperative analgesic effects of intravenous ibuprofen versus ketorolac in children undergoing open unilateral lower abdominal surgery. The authors hypothesized that postoperative analgesia produced by intravenous ibuprofen would be non-inferior to that of intravenous ketorolac. METHODS: Sixty-six children aged 2 to 8 years who were scheduled to undergo unilateral lower abdominal surgery, were recruited. Patients in the ibuprofen group received 10mg/kg/6h intravenous ibuprofen. Patients in the ketorolac group were given 0.5mg/kg/6h intravenous ketorolac. The primary outcome measure was 24-h postoperative morphine consumption. The secondary outcome measures were postoperative pain score, the incidence of early postoperative fever and the incidence of ibuprofen and ketorolac adverse effects including pain during drug infusion, vomiting, epigastric pain and allergic reaction. RESULTS: Fifty-nine patients completed the study (30 ibuprofen, 29 ketorolac). There was no significant difference (P=0.305) in the mean (SD) 24-h postoperative morphine consumption (µ/kg) between intravenous ibuprofen, 16.00 (5.31), and ketorolac, 14.65 (4.61). The reported pain scores were similar in both groups. The incidence of postoperative fever was significantly lower (p=0.039) in the ibuprofen group (3%) than the ketorolac group (20%). The incidence of adverse effects was similar in both ibuprofen and ketorolac groups. CONCLUSIONS: Intravenous ibuprofen can be used as an alternative to ketorolac for postoperative analgesia in children undergoing unilateral lower abdominal surgery because both drugs similarly provide safe and effective postoperative analgesia.
Subject(s)
Analgesia , Tolmetin , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Child , Double-Blind Method , Humans , Ibuprofen/therapeutic use , Ketorolac/therapeutic use , Morphine/therapeutic use , Pain, Postoperative/drug therapy , Tolmetin/adverse effectsABSTRACT
AIM: In order to avoid gastric irritation caused by tolmetin sodium (TS), gastro resistant Eudragit® S 100 microsphere formulations were prepared with the emulsion/solvent diffusion method. MATERIALS: Considering the high water solubility of the TS molecule, the effects of the presence of inorganic salt (NaCl, NaBr and KH2PO4; 0.1 M and 1.0 M) in external phase and external phase pH on the encapsulation efficiency were evaluated. RESULTS: Percentage yield value was found to vary between 55.8% and 72.1%. Improvement in encapsulation efficiency was determined by increasing concentrations of NaCl, NaBr and KH2PO4. The microspheres were observed to have a spherical shape and the measured particle size values varied between 52.1 and 81.5 µm. The released amounts of the drug were found to be low as the inorganic salt concentrations increased. CONCLUSION: Conclusively, drug release in stomach pH was significantly prevented by the microspheres prepared using Eudragit® S 100 polymer, and these formulations are considered to be a model for other orally administered drugs with similar problems.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Microspheres , Polymethacrylic Acids/chemistry , Tolmetin/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Chemistry, Pharmaceutical , Diffusion , Emulsions , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Particle Size , Salts/chemistry , Solubility , Solvents/chemistry , Tolmetin/adverse effects , Tolmetin/chemistrySubject(s)
Anaphylaxis , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Death , Hallucinations , Tolmetin/analogs & derivatives , Adult , Anaphylaxis/etiology , Anaphylaxis/therapy , Anti-Inflammatory Agents/administration & dosage , Cardiopulmonary Resuscitation , Humans , Injections, Intravenous , Male , Methylprednisolone Hemisuccinate/administration & dosage , Tolmetin/adverse effectsABSTRACT
BACKGROUND: The arthritis of rheumatic fever is very responsive to treatment with salicylates, but there are many adverse reactions, especially hepatotoxicity, due to aspirin (acetylsalicylic acid) therapy. These side-effects change the course and duration of rheumatic fever. Other non-steroidal anti-inflammatory drugs may be equally effective, although no reports are available. METHODS: We studied 72 patients with rheumatic fever who were admitted to Dr Sami Ulus Children's Hospital between 1995 and 1999. Twenty patients with arthritis were treated with tolmetin (25 mg/kg per day; group I) and 52 patients with arthritis and/or mild carditis were put on aspirin therapy (75-100 mg/kg per day) for 4-6 weeks (group II). Arthritis had disappeared at the same time in both the aspirin and tolmetin groups (P = 0.675). RESULTS: The erythrocyte sedimentation rates of patients upon admission, at the first week and at the end of therapy were not different in the two groups (P > 0.05). No adverse effect of tolmetin therapy was observed, whereas side-effects of salicylate were observed in 19 patients (36.5%) in the aspirin group. Hepatotoxicity, gastric irritation and salicylism were found in 16, four and three patients, respectively. Renal toxicity and Reye syndrome were not demonstrated. Because of these side-effects of aspirin, therapy had to be stopped for 10-20 days and the duration of hospitalization in this group was lengthened unnecessarily. CONCLUSION: Tolmetin was safe and effective treatment for arthritic rheumatic fever patients without carditis. Tolmetin can be used particularly in patients who cannot tolerate aspirin.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Rheumatic Fever/drug therapy , Tolmetin/therapeutic use , Adolescent , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Child , Child, Preschool , Female , Humans , Infant , Male , Tolmetin/adverse effectsABSTRACT
The control of postoperative pain in the pediatric orthopaedic patient is a challenging endeavor. Several studies have shown the efficacy of ketorolac tromethamine in the pediatric general surgical population, but its efficacy in the pediatric orthopaedic population remains unproven. Twenty-seven consecutive patients (age 6 months to 18 years) who underwent long-bone osteotomies or foot procedures by a group of three pediatric orthopaedic surgeons were given a ketorolac protocol (1 mg/kg loading, 0.5 mg/kg every 6 h for 24 h). Breakthrough pain was managed with morphine until the patient was able to take oral pain medication, as was any pain after the 24-h period for ketorolac expired. Thirty-seven age- and case-matched patients were used as retrospective controls. The patients in the study who received ketorolac required significantly fewer doses of morphine than did the control group (2.29 +/- 3.98 vs. 10.02 +/- 3.39; p < 0.05). In addition the patients on the ketorolac protocol experienced fewer gastrointestinal side effects (4% vs. 32%; p < 0.05). Finally, the patients in the ketorolac group had a significantly shorter length of stay (3.63 +/- 1.64 days vs. 4.74 +/- 1.76 days; p < 0.05). There were no bleeding complications in either group. Ketorolac is thus a safe and effective means of controlling postoperative pain in the pediatric orthopaedic population while avoiding the troubling maleffects seen with the exclusive use of morphine.
Subject(s)
Analgesics, Non-Narcotic , Clubfoot/surgery , Length of Stay , Osteotomy , Pain, Postoperative/prevention & control , Tolmetin/analogs & derivatives , Tromethamine/analogs & derivatives , Adolescent , Adult , Analgesics, Non-Narcotic/adverse effects , Child , Child, Preschool , Gastrointestinal Diseases/chemically induced , Humans , Infant , Ketorolac Tromethamine , Matched-Pair Analysis , Orthopedic Procedures , Tolmetin/adverse effects , Tromethamine/adverse effectsABSTRACT
AIM: To compare the analgesic efficacy and toxicity of the nonsteroidal anti-inflammatory analgesic drug, ketorolac (Toradol, Recordati spa, Milan) 10 mg p.o. (t.i.d.) with diclofenac (Voltaren, Novartis Farma, Origglo, VA) 50 mg p.o. (t.i.d.) in cancer patients with moderate to severe chronic pain. METHODS AND STUDY DESIGN: The study was a multicenter randomized double-blind cross-over trial. Each treatment lasted 7 days, after which the patients crossed over to the other drug. Pain intensity was evaluated by the visual analogue scale (VAS) after the first dose and by the 5-point verbal rating scale (VRS) by the patient and by the physician following the 7-day treatment. RESULTS AND CONCLUSIONS: A total of 138 advanced cancer patients were enrolled in the study. Overall 251 single-dose administrations (117 cross-over observations) and 257 multiple treatments (127 cross-over experiments) were assessable. After a single administration of ketorolac and diclofenac, no significant difference could be observed in analgesic activity, as indicated by the area under the pain-intensity time curve (AUC0-8), in the maximum efficacy, or the duration of efficacy of the two drugs. The Westlake confidence intervals of the AUC0-8 ratio (ketorolac: diclofenac) (1.07; 90% CI, 0.94-1.19), of the maximum efficacy ratio (1.03; 90% CI, 0.92-1.14), and the duration of efficacy ratio (1.05; 90% CI, 0.97-1.11) showed the bioequivalence of the two drugs. Satisfactory pain relief was reported for multiple 7-day treatments, with no significant differences between the two therapies: according to the physician's evaluation, in 93/128 (73%; 95% CI, 65-80%) ketorolac treatments and 91/129 (71%; 95% CI, 63-78%) diclofenac treatments; according to the patient's evaluation, in 83/128 cases (65%; 95% CI, 57-73%) after ketorolac and in 74/129 cases (57%; 95% CI, 49-66%) after diclofenac. Adverse symptoms were acceptable with both drugs. Interestingly, a pronounced sequence effect was found: gastric disturbances after ketorolac were observed mainly (10 out of 15 observed events) when the drug was given to patients pretreated with diclofenac.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diclofenac/therapeutic use , Neoplasms/complications , Pain/drug therapy , Tolmetin/analogs & derivatives , Administration, Oral , Adult , Aged , Analgesics, Non-Narcotic/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Area Under Curve , Cross-Over Studies , Diclofenac/adverse effects , Double-Blind Method , Drug Administration Schedule , Female , Humans , Ketorolac Tromethamine , Male , Middle Aged , Pain/etiology , Therapeutic Equivalency , Tolmetin/adverse effects , Tolmetin/therapeutic useABSTRACT
Nonsteroidal anti-inflammatory drugs are often used in the management of those with acute pain secondary to sickle cell disease due to potent analgesic effects along with a lack of addictive potential, respiratory depression, and central nervous system effects, as may occur with narcotics. Caution should be observed in the use of nonsteroidal anti-inflammatory drugs in patients with compromised renal function. We present a case of a 17-year-old sickle cell disease patient with an acute painful episode and normal renal function indices who subsequently developed irreversible renal failure and a perirenal hematoma following the administration of ketorolac, despite adequate hydration. Due to its inhibitory effect on prostaglandin-mediated vasodilation, we advise caution in the use of ketorolac for the pain management of sickle cell painful episodes. We recommend following the administration guidelines for ketorolac for renal-compromised patients in those with painful episodes of sickle cell disease, and if used in this patient population, renal function must be very closely monitored.
Subject(s)
Anemia, Sickle Cell/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Renal Insufficiency/chemically induced , Tolmetin/analogs & derivatives , Adolescent , Female , Humans , Ketorolac , Tolmetin/adverse effectsABSTRACT
Recent reports have associated an increased incidence of bleeding after tonsillectomy with the perioperative use of ketorolac tromethamine. To review this association, we examined the hospital and office records of 310 pediatric patients who underwent tonsillectomy with or without adenoidectomy at our institution during a 2-year period. Of these patients, 213 received ketorolac administered as a single dose at the conclusion of the procedure. The remaining 97 patients did not receive ketorolac. The frequency of postoperative hemorrhage was not found to differ significantly between these 2 groups (2.3% vs. 3.1% respectively, P = 0.71). Furthermore, the average time to discharge after surgery was significantly shorter in those patients who received ketorolac than in those who did not (8.5 hours vs. 12.5 hours, respectively, P < 0.0001). The frequency of overnight hospital stays was also significantly lower in those patients who received ketorolac (16.0% vs. 31.6%, respectively, P < 0.01). Concern over the potential for increased hemorrhage after tonsillectomy has led several authors to caution against the use of ketorolac in this setting. In our study, however, the use of ketorolac was not found to increase the incidence of posttonsillectomy hemorrhage and furthermore was associated with a significant decrease in the length of hospital stay as well as a decreased likelihood of overnight hospital stay after surgery.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Postoperative Hemorrhage/etiology , Tolmetin/analogs & derivatives , Tonsillectomy/adverse effects , Tromethamine/analogs & derivatives , Adenoidectomy , Adolescent , Child , Child, Preschool , Female , Humans , Incidence , Intraoperative Care , Ketorolac Tromethamine , Length of Stay/statistics & numerical data , Male , Retrospective Studies , Severity of Illness Index , Tolmetin/adverse effects , Tromethamine/adverse effectsSubject(s)
Analgesics, Non-Narcotic/immunology , Aspirin/immunology , Drug Hypersensitivity/etiology , Medication Errors/prevention & control , Tolmetin/analogs & derivatives , Analgesics, Non-Narcotic/adverse effects , Aspirin/adverse effects , Asthma/chemically induced , Cross Reactions , Drug Interactions , Humans , Ketorolac , Male , Middle Aged , Pain/drug therapy , Tolmetin/adverse effects , Tolmetin/immunologyABSTRACT
Pain and its treatment are known to have adverse effects on the organism, including deterioration in myocardial, diaphragmatic, and small bowel function. The provision of adequate intravenous analgesia, and the choice of agent, can ameliorate or exacerbate these manifestations of the stress response. The choice of agent, opioid or non-opioid, has in some respects become more difficult as more information has become available regarding the merits and adverse effects of each. Increased awareness of the frequency of hypoxemia secondary to the opioids' ability to cause an obstructive sleep apnea picture, and the cost efficiency of ketorolac through a reduction in opioid toxicity, contrast with recent studies which suggest that the gastrotoxic and nephrotoxic effects of ketorolac may occur earlier than previously suspected. The suitability of using the dissociative anesthetic agent ketamine in critically ill patients remains to be proven. Ketamine provides intense analgesia at subanesthetic doses. Its centrally mediated sympathomimetic action encourages hemodynamic stability, and it is relatively devoid of respiratory depressant activity. Increasing experience with ketamine outside the operating room has resulted in its successful use in cases of severe bronchospasm and status epilepticus.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Analgesics, Opioid/therapeutic use , Anesthetics, Dissociative/therapeutic use , Critical Care/methods , Ketamine/therapeutic use , Pain/prevention & control , Tolmetin/analogs & derivatives , Analgesics, Non-Narcotic/adverse effects , Anesthetics, Dissociative/pharmacokinetics , Humans , Injections, Intravenous , Ketamine/pharmacokinetics , Ketorolac , Tolmetin/adverse effects , Tolmetin/therapeutic useABSTRACT
PURPOSE: To investigate the efficacy and safety of nonpreserved ketorolac tromethamine 0.5% ophthalmic solution in relieving pain following radial keratotomy (RK). SETTING: Multicenter clinical trial. METHODS: Topical ketorolac was compared with its vehicle in a double-masked, randomized, parallel-group study involving 170 RK patients. Patients were treated with nonpreserved ketorolac 0.5% ophthalmic solution or the vehicle 4 times daily beginning immediately after surgery and continuing for 3 days or until they no longer had ocular pain. RESULTS: At several intervals, patients treated with ketorolac reported significantly greater pain relief and less pain intensity than patients treated with the vehicle. The time required for patients to first report "complete relief" or "no pain" was shorter in the ketorolac than in the vehicle group (P < or = .006). Patients in the ketorolac group used less escape medication (acetaminophen) (P < or = .001) and had fewer sleep difficulties (P < or = .031), fewer symptoms of ocular discomfort (P < or = .028), and less difficulty performing activities of daily living (P = .048). Patients treated with ketorolac experienced the same low rate of treatment-related adverse events as those treated with the vehicle and exhibited the same improvement in visual acuity and manifest refraction. CONCLUSIONS: Nonpreserved ketorolac tromethamine 0.5% ophthalmic solution was significantly more effective than, and as safe as, the vehicle in alleviating the postoperative pain associated with RK. This resulted in significant improvements in patient quality of life and less need for oral analgesics, suggesting that topical ketorolac is an appropriate treatment option for ocular pain following RK.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Keratotomy, Radial/adverse effects , Pain, Postoperative/drug therapy , Tolmetin/analogs & derivatives , Tromethamine/analogs & derivatives , Adolescent , Adult , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Double-Blind Method , Female , Humans , Ketorolac Tromethamine , Male , Middle Aged , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/adverse effects , Ophthalmic Solutions/therapeutic use , Pain, Postoperative/etiology , Preservatives, Pharmaceutical , Quality of Life , Safety , Tolmetin/administration & dosage , Tolmetin/adverse effects , Tolmetin/therapeutic use , Treatment Outcome , Tromethamine/administration & dosage , Tromethamine/adverse effects , Tromethamine/therapeutic useABSTRACT
BACKGROUND: We evaluated the efficacy and safety of ketorolac (Toradol). METHODS: In this prospective trial, 88 women in confirmed preterm labor at < or =32 weeks' gestation were randomized to receive magnesium sulfate given as an initial 6 g intravenous bolus followed by continuous infusion therapy (2 to 6 g/hr) or intramuscularly administered ketorolac (60 mg loading dose) followed by 30 mg every 6 hours for a maximum of 24 hours. RESULTS: The study groups were similar with respect to age, parity, cervical status, and gestational age on admission. Ketorolac was more rapid (2.71 hr+/-2.16) in the arrest of preterm labor than was magnesium sulfate (6.22 hr+/-5.65). No patient required discontinuance of either drug due to adverse effects. There was no difference in the incidence of neonatal complications between the two groups. CONCLUSION: In gestations with preterm labor at <32 weeks, ketorolac appears to be an appropriate first-line tocolytic agent.
Subject(s)
Magnesium Sulfate/administration & dosage , Obstetric Labor, Premature/prevention & control , Tocolysis , Tocolytic Agents/administration & dosage , Tolmetin/analogs & derivatives , Adult , Birth Weight , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature, Diseases/etiology , Infusions, Intravenous , Injections, Intramuscular , Ketorolac Tromethamine , Magnesium Sulfate/adverse effects , Pregnancy , Prospective Studies , Tocolytic Agents/adverse effects , Tolmetin/administration & dosage , Tolmetin/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Dextran may be used in surgical patients for thromboprophylaxis or volume expansion along with ketorolac, a nonsteroidal anti-inflammatory drug, for analgesia. As these two agents can influence the haemostatic system at different sites, it is important to demonstrate that there is no adverse haemostatic interaction between them. METHODS: The haemostatic interaction between intravenous dextran-70 and intramuscular ketorolac was assessed in a double-blind, randomised, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo intramuscularly and dextran/placebo intravenously. The effect of ketorolac and dextran on haemostasis was assessed by the following techniques: skin bleeding time, in vitro platelet aggregation function, whole blood thromboxane generation, von Willebrand factor antigen, factor VIII coagulant activity and tissue plasminogen activator. The results were analysed for the effects of ketorolac and dextran and for any evidence of an interaction. RESULTS: Ketorolac inhibited platelet function and thromboxane generation. Dextran reduced factor VIII coagulant activity. Neither agent had a significant effect on bleeding time, von Willebrand factor or tissue plasminogen activator. There was only evidence of a small but statistically significant interaction between ketorolac and dextran on thromboxane generation. There was no evidence of any other interaction of ketorolac with dextran. CONCLUSION: This interaction on thromboxane generation is unlikely to be of clinical significance as substantial inhibition of thromboxane generation occurs with ketorolac alone.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Dextrans/pharmacology , Hemostasis/drug effects , Hemostatics/pharmacology , Tolmetin/analogs & derivatives , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Bleeding Time , Cross-Over Studies , Dextrans/administration & dosage , Dextrans/adverse effects , Double-Blind Method , Drug Interactions , Hemostatics/administration & dosage , Hemostatics/adverse effects , Humans , Injections , Ketorolac , Male , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Thromboxane B2/blood , Tolmetin/administration & dosage , Tolmetin/adverse effects , Tolmetin/pharmacologyABSTRACT
OBJECTIVE: Ketorolac tromethamine 0.5% and diclofenac sodium 0.1% ophthalmic solutions are approved for use by the U.S. Food and Drug Administration to avoid excessive postoperative inflammation after cataract surgery and implantation of an intraocular lens. This study compares the efficacy and toxicity of these nonsteroidal anti-inflammatory drugs for the first time. DESIGN: Randomized, double-masked, prospective clinical trial. PARTICIPANTS: A total of 120 patients assigned in equal numbers to 1 of the 2 treatment regimens. INTERVENTION: Treatment with either ketorolac 0.5% or diclofenac 0.1% ophthalmic solutions instilled four times daily for 30 days beginning the first postoperative day after surgery. MAIN OUTCOME MEASURES: Objective (Kowa FC 1000 laser cell and flare meter) and subjective (slit-lamp biomicroscope) measurements of inflammation and toxicity were made and compared at three separate post-operative visits. RESULTS: The anti-inflammatory effects of the two treatment regimens were not statistically different at any of the postoperative visits. Patients tolerated both treatments equally well. CONCLUSIONS: This study shows diclofenac sodium 0.1% and ketorolac tromethamine 0.5% ophthalmic solutions are equally effective and safe for the control of postoperative inflammation after uncomplicated cataract surgery performed by phacoemulsification followed by the implantation of a foldable intraocular lens.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Diclofenac/administration & dosage , Phacoemulsification/adverse effects , Tolmetin/analogs & derivatives , Tromethamine/analogs & derivatives , Uveitis, Anterior/prevention & control , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Diclofenac/adverse effects , Double-Blind Method , Female , Humans , Inflammation/etiology , Inflammation/prevention & control , Ketorolac Tromethamine , Lens Implantation, Intraocular/adverse effects , Male , Middle Aged , Ophthalmic Solutions , Prospective Studies , Safety , Tolmetin/administration & dosage , Tolmetin/adverse effects , Treatment Outcome , Tromethamine/administration & dosage , Tromethamine/adverse effects , Uveitis, Anterior/etiologyABSTRACT
STUDY OBJECTIVE: To determine the effect of dilution with intravascular volume expanders commonly used by anesthesiologists on clinically relevant levels of free serum ketorolac. DESIGN: In vitro study. SETTING: Pharmaceutics laboratory of a medical college. INTERVENTIONS: The effect of 6% hydroxyethylstarch, 5% albumin, 6% dextran 60, and lactated Ringer's solution on in vitro plasma protein binding of ketorolac was investigated by ultrafiltration. The binding was studied at three different drug concentrations: low therapeutic (0.3 microgram/ml), high therapeutic (3 micrograms/ml), and toxic (10 micrograms/ml), and at two or more volume expander dilutions. MEASUREMENTS AND MAIN RESULTS: The effect of plasma dilution on free ketorolac was consistent across all volume expanders tested and for each ketorolac concentration studied. As the plasma dilution with albumin, hydroxyethylstarch, dextran 60, or lactated Ringer's solution increased, the unbound ketorolac also increased from 3.2% to 3.3% in undiluted plasma to 5.0% to 8.7% in 50% dilution of the plasma with the investigated expanders. Dilution of plasma by only 10% resulted in a significant, but relatively minor, increase of unbound ketorolac to 3.2% to 3.8%. CONCLUSION: Because of the pharmacokinetic properties of ketorolac, this pharmacokinetic interaction can be expected to have only minor effects on unbound ketorolac concentrations when ketorolac is administered after the plasma expander. When ketorolac administration is followed by rapid plasma expander infusion, a transient increase of unbound ketorolac in plasma can be expected.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/metabolism , Blood Proteins/metabolism , Plasma Substitutes/pharmacology , Tolmetin/analogs & derivatives , Humans , Ketorolac , Protein Binding , Tolmetin/adverse effects , Tolmetin/metabolismABSTRACT
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 hr 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.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Pain, Postoperative/prevention & control , Premedication , Tolmetin/analogs & derivatives , Tonsillectomy , Acetaminophen/administration & dosage , Acetaminophen/therapeutic use , Adolescent , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Child , Child, Preschool , Double-Blind Method , Evaluation Studies as Topic , Female , Follow-Up Studies , Humans , Incidence , Injections, Intravenous , Ketorolac , Male , Pain Measurement , Placebos , Postoperative Complications/prevention & control , Postoperative Hemorrhage/etiology , Safety , Tolmetin/administration & dosage , Tolmetin/adverse effects , Tolmetin/therapeutic use , Vomiting/prevention & controlABSTRACT
Acute low back pain is a common problem in the emergency department (ED). Effective management of acute pain enhances early rehabilitation and recovery. Given the importance of inflammatory mediators in pain generation and the adverse effects associated with opioids, it is logical to expect that a non-opioid agent with antiinflammatory and analgesic properties would provide excellent analgesia with fewer adverse effects. This double-blind, randomized, multicenter clinical trial, performed in six university and community hospital EDs, compares the analgesic efficacy and adverse effects of ketorolac to those of acetaminophen-codeine in ED patients with acute musculoskeletal low back pain. Our hypothesis was that ketorolac would provide superior analgesia with fewer adverse effects. One hundred twenty-three patients with acute low back pain were randomized to receive ketorolac (KET, N = 63) or acetaminophen-codeine (ACOD, N = 60). Most (79%) were males, and the mean age was 34.5 years. After baseline clinical assessment, patients were treated with ketorolac (10 mg every 4 to 6 h as needed, up to four daily doses) or acetaminophen-codeine (600 mg-60 mg, respectively, every 4 to 6 h as needed, up to six daily doses) and followed for one week. Pain intensity was assessed on visual analogue and categorical scales. Functional capacity, overall pain relief, and overall medication rating were assessed on categorical scales. Adverse events were documented. Primary outcomes included: 1) Pain intensity differences, based on visual analogue scores, for the 0 to 6 h treatment phase. 2) Incidence of adverse events. Secondary outcomes included analgesic efficacy, functional capacity, and overall subjective drug evaluation at one week. Both drugs provided substantial pain relief, with maximal effect 2.2 h after oral dosing. There were no significant differences in analgesic efficacy, functional capacity, or overall pain relief between the two groups. Sixteen patients (10 KET vs. 6 ACOD, NS) withdrew prematurely because of drug inefficacy. Patients in the ACOD group reported significantly more adverse drug events and serious adverse drug events. Seven patients--all in the ACOD group--withdrew from the study because of adverse drug events. Based on comparable efficacy and a superior adverse event profile, ketorolac was preferable to acetaminophen with codeine for the treatment of acute low back pain in the ED.
Subject(s)
Acetaminophen/administration & dosage , Analgesics, Non-Narcotic/therapeutic use , Analgesics, Opioid/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Back Pain/drug therapy , Codeine/administration & dosage , Cyclooxygenase Inhibitors/therapeutic use , Tolmetin/analogs & derivatives , Acetaminophen/adverse effects , Acute Disease , Adolescent , Adult , Analgesics, Non-Narcotic/administration & dosage , Back Pain/rehabilitation , Codeine/adverse effects , Cyclooxygenase Inhibitors/adverse effects , Double-Blind Method , Drug Combinations , Drug Tolerance , Emergencies , Female , Humans , Ketorolac , Male , Middle Aged , Pain Measurement , Tolmetin/adverse effects , Tolmetin/therapeutic useABSTRACT
UNLABELLED: This randomized, blind study was designed to determine the appropriate dose of ketorolac (a drug used as a supplement to opioids) to administer to patients who have undergone spinal stabilization surgery. The ketorolac was administered every 6 h, in addition to patient-controlled analgesia (PCA) with morphine, to 70 inpatients undergoing spine stabilization by one surgeon. The study was performed to determine the analgesic efficacy and incidence of side effects with different doses of ketorolac. The patients were divided into seven groups. They were given either i.v. saline (control group) or i.v. ketorolac (5, 7.5, 10, 12.5, 15, or 30 mg) every 6 h. The outcomes measured included pain scores, 24-h morphine usage, level of sedation, and side effect profile six times during the first 24 h postoperatively. The total dose of morphine was significantly larger in the control and 5 mg ketorolac groups than in the other five groups. Morphine consumption was similar in all groups receiving > or = 7.5 mg of ketorolac. The pain scores were significantly higher in the control group than in some of the larger dose groups at three of the study intervals. The 5 mg group had higher pain scores than the other groups at most of the time intervals studied. There were no significant differences in pain scores among the other five groups. Sedation scores were higher (i.e., patients were more sedated) in the control group than in the other six groups at three of the time periods. We conclude that the administration of ketorolac 7.5 mg every 6 h has a morphine-sparing effect equivalent to that of larger doses in patients undergoing spine stabilization surgery. Using larger doses of ketorolac did not result in less somnolence, lower morphine use, or less pain. We recommend that ketorolac 7.5 mg be given every 6 h to patients undergoing spinal fusion surgery in addition to PCA morphine. IMPLICATIONS: Using smaller doses of ketorolac (e.g., 7.5 mg every 6 h) as a supplement to morphine patient-controlled analgesia is as effective as larger doses in patients who have undergone spine stabilization surgery.