Comparison of electromotive drug administration with ketorolac or with placebo in patients with pain from rheumatic disease: a double-masked study

This study was undertaken to assess the efficacy of ketorolac compared with placebo when delivered by electromotive drug administration (EMDA) in patients with pain from rheumatic disease. In EMDA, or iontophoresis, a low-intensity electric current is applied over the skin to deliver medication into body tissues. Although EMDA has been used to treat patients with various diseases, controlled studies are lacking in patients with rheumatic disease. This double-masked study included 60 patients (43 women and 17 men) aged 31 to 80 years with the following conditions: 12, epicondylitis; 30, scapulohumeral periarthritis; 10, gonalgia; and 8, metatarsalgia. They were divided randomly by a physician into 2 groups of 30 patients each for 5 sessions of active treatment (30 mg of ketorolac) or placebo (5 mL of normal saline). Treatment took place every other day for 20 minutes. Immediately before and after the five treatment sessions and 7 days after treatment ended, both patient and physician measured the degree of pain using a categoric scale (no pain, slight pain, intermediate pain, strong pain, and very strong pain) and evaluated pain intensity using the Scott and Huskisson Visual Analogue Scale (VAS). Seven days after treatment ended, both physician and patient judged the result of treatment using a second categoric scale (no improvement or intermediate, good, or very good result). Both ketorolac and placebo provided immediate, significant pain relief when delivered by EMDA, but only those patients receiving ketorolac experienced a further reduction in pain 7 days after treatment; those receiving placebo experienced a slight increase in pain. VAS values differed significantly between the two groups. Poor results (no improvement) were significantly higher in the placebo-treated group, while good results were significantly higher in the ketorolac-treated group. No patient reported any adverse effects during treatment. This study demonstrates that ketorolac relieves pain when delivered by EMDA and offers longer-lasting pain relief than does placebo.     

The clinical characteristics of intraoral herpes simplex virus infection in 52 immunocompetent patients

OBJECTIVES: To determine if nonsteroidal anti-inflammatory drugs provide adequate pain control for patients having laparoscopic hernia repair and to compare the effectiveness of ketorolac tromethamine with ibuprofen in reducing postoperative laparoscopic hernia pain. DESIGN AND SETTING: Prospective double-blind randomized study at a 100-bed community hospital. PATIENTS: Seventy patients ranging in age from 16 to 83 years scheduled for elective laparoscopic inguinal hernia repair. INTERVENTIONS: Patients undergoing laparoscopic hernia repair were enrolled in a double-blind randomized study to compare the 2 treatments. Group 1 received a placebo capsule 1 hour before surgery and ketorolac tromethamine, 60 mg intravenously, at the time of trocar insertion. Group 2 received ibuprofen, 800 mg an hour before surgery, and isotonic sodium chloride solution, 2 mL intravenously, at the time of trocar insertion. In addition, all patients received local infiltration of 30 mL of bupivacaine hydrochloride into their trocar sites. All patients were discharged within 5 hours of the operation and were instructed to take 400 mg of ibuprofen orally every 4 hours for 24 hours whether or not they were experiencing pain. A 24-hour supply of ibuprofen was provided to all study patients. Pain was assessed using the Visual Analog Pain Scale with a maximum pain rating of 100. Assessments were done at the time of and 18 hours after discharge. MAIN OUTCOME MEASURE: Postoperative pain 18 and 24 hours after discharge was assessed using a standardized questionnaire in a telephone interview by a registered nurse from the Outpatient Surgical Unit. RESULTS: There was no significant difference in the level of pain experienced by 35 patients who received ketorolac intravenously and 35 who received ibuprofen orally. There was no significant difference between the 2 treatment groups in the amount of pain experienced at discharge and 18 hours after discharge. CONCLUSIONS: Pain relief from ibuprofen, 800 mg, administered orally an hour before laparoscopic hernia repair was not statistically different from that obtained with intravenous ketorolac, 60 mg, administered intraoperatively when comparing the hospital discharge pain score and the mean and highest pain scores 18 hours after discharge. Ibuprofen offers equivalent pain control at a lower cost and reduced potential for adverse drug events compared with intravenous ketorolac in patients having laparoscopic hernia repair. No patient required narcotic supplementation, and pain control was judged satisfactory by all the patients.     

Ketorolac and propofol administration for prevention of nausea and vomiting in patients undergoing minor gynecologic surgery

This clinical review explores the efficacy of the nonsteroidal antiinflammatory agent, ketorolac tromethamine, added to an anesthetic regimen utilizing intravenous propofol. Both agents have been shown to reduce the incidence of nausea and vomiting postoperatively when administered to patients undergoing minor gynecologic surgery. Because the incidence of nausea and vomiting is significantly reduced when ketorolac is used in place of opioids to attenuate postoperative pain, it would appear to be an appropriate choice of agent to use following propofol anesthesia. The use of this combination of drugs may not only reduce the incidence of postoperative nausea and vomiting in patients undergoing minor gynecologic surgery, but could reduce the duration of hospitalization and enhance recovery from anesthesia.     

Ondansetron versus droperidol or placebo to prevent nausea and vomiting after otologic surgery

This study compares the preoperative administration of ondansetron with that of droperidol or saline solution for the prevention of nausea and vomiting in otologic surgery patients. A total of 120 otherwise healthy individuals were randomly assigned to receive either saline solution, ondansetron (4 mg intravenously), or droperidol (25 microg/kg intravenously) before anesthetic induction. Intraoperative and postanesthesia care unit times were recorded along with incidence of nausea, vomiting, pain, nausea and recovery scores, and the administration of rescue antiemetics. Similar assessments were made during the next 24 hours. Demographics were similar, but more males received ondansetron. Anesthetic recovery scores were lower after administration of droperidol than after ondansetron. Incidence of nausea was similar between groups, but severity was greater with placebo and droperidol than with ondansetron. More vomiting occurred with placebo than with ondansetron or droperidol. No intergroup differences in rescue antiemetic administration were noted, however. Twenty-four hours later, more patients receiving placebo had nausea or vomited than patients receiving droperidol or ondansetron. Fewer women in the ondansetron group vomited than in the other two groups. Ondansetron 4 mg intravenously is as effective as droperidol and better than saline solution in preventing nausea and vomiting in patients undergoing otologic surgery. No cost advantage as determined by lower use of rescue antiemetics or shorter postanesthesia care unit times was noted after ondansetron therapy.     

Subtalar staple arthroereisis for planovalgus foot deformity in children with neuromuscular disease

This double-blinded study was undertaken to prospectively evaluate the role of halothane and sevoflurane and the use of IV ketorolac on the anesthetic emergence in a group of children undergoing bilateral myringotomy with pressure equalization tube procedures. Two-hundred ASA physical status I and II patients were premedicated with nasal midazolam (0.2 mg/kg) and randomized to one of four groups (Group 1 - halothane and ketorolac; Group 2 - halothane and placebo; Group 3 - sevoflurane and ketorolac; Group 4 - sevoflurane and placebo). A blinded nurse observer characterized the quality of the anesthetic emergence and recorded the incidence of emesis and the use of pain medications in the recovery room. There were no differences in age, weight, previous anesthetic experience, or duration of anesthesia among the four groups. There was no difference in the incidence of emergence agitation for patients anesthetized with sevoflurane compared with halothane, regardless of whether they received ketorolac or placebo. Regardless of the anesthetic, the incidence of emergence agitation was significantly less in patients who received ketorolac compared with patients who received placebo. The incidence of emesis in the recovery room, the total 24-h incidence of emesis, and the use of at-home pain medications were similar in all four groups. IMPLICATIONS: We conclude that the incidence of emergence agitation in children undergoing ultrashort anesthetic procedures is similar for sevoflurane and halothane and that ketorolac markedly diminishes emergence agitation and/or pain behavior.     

Does the preoperative administration of ketorolac improve postoperative analgesia

AIM OF THE STUDY: 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. DESIGN: Prospective randomized trial. SETTING: University surgical department. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Interposed bone grafts to accommodate endosteal implants for retaining mandibular overdentures. A 1-7 year follow-up study

STUDY OBJECTIVES: To examine the effect of timing of an intravenous (i.v.) dose (intraoperative vs. postoperative) of ketorolac tromethamine on pain scores and overall outcome after total abdominal hysterectomy (TAH) and myomectomy. DESIGN: Prospective, randomized, placebo-controlled study. PATIENTS: 248 ASA physical status I and II adult female patients scheduled for elective hysterectomy or myomectomy. INTERVENTIONS: General anesthesia was administered that consisted of thiopental sodium for induction, enflurane or isoflurane in nitrous oxide-oxygen for maintenance, and small doses of fentanyl and midazolam. Patients were randomized into three groups to receive toradol/placebo on a dosing schedule of dose 1 given one-half hour prior to expected end of surgery, dose 2 given on awakening in the postanesthesia care unit, and doses 3, 4, and 5 given at 6, 12, and 18 hours, respectively, after dose 2; Group 1 patients received placebo (saline) for dose 1, ketorolac 60 mg i.v. for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 2 patients received ketorolac 60 mg i.v. for dose 1, placebo for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 3 patients received placebo for all doses. All patients were given i.v. morphine PCA postoperatively, and morphine usages, visual analog pain intensity (VAS) scores, as well as adverse events and median times to recovery milestones were recorded. MEASUREMENTS AND MAIN RESULTS: VAS scores (mean) before dose 2 were significantly lower in Group 2 than Group 1, as were at-rest evaluations at 15 minutes and one hour. Group 2 patients also had decreased morphine requirements as compared to placebo. Both ketorolac groups (Groups 1 and 2) had significantly higher values for patient and observer overall ratings, case of nursing care, and tolerability as compared to placebo (Group 3). There were no significant differences among groups in adverse events or median times to recovery milestones. CONCLUSIONS: Although it is possible to demonstrate an improvement in early postoperative pain scores with intraoperative ketorolac and better overall ratings of ketorolac both intraoperatively and postoperatively as compared with placebo, the lack of clinically significant differences in analgesic efficacy in the two active study groups indicates the need for a careful consideration by the clinician of the risks versus benefits involved in the administration of antiplatelet medication in the perioperative period.     

A single dose of morphine sulfate increases the incidence of vomiting after outpatient inguinal surgery in children

BACKGROUND: In children, opioids are valuable both for their analgesic properties and for their salutary effect on emergence delirium. Although intraoperative administration of opioids is often cited as the cause of postoperative emesis, few data quantitating the magnitude of this effect exist. METHODS: Patients undergoing inguinal surgery as outpatients were randomly assigned to one of two groups. One group received a single intravenous dose of morphine 0.1 mg/kg (morphine group), and the other (control) group had the identical anesthetic but instead received saline. Intravenous ketorolac was administered in response to verbal complaints of pain or a Children's Hospital of Eastern Ontario Pain Score greater than 9 on two successive evaluations performed at 5-min intervals. The authors compared the incidence of postoperative emesis and emergence, behavior, and pain scores between the two groups. RESULTS: Patients in the morphine group (n = 48) were 5.6 +/- 2.8 yr old and weighed 20.8 +/- 7.8 kg, and those in the control group (n = 49) were 4.5 +/- 2.9 yr old and weighed 18.9 +/- 9.2 kg. More patients in the morphine group were cooperative and deeply asleep both on arrival and through the first 30 min of their stay in the postanesthesia care unit (PACU) (P < 0.05). Sixty-three percent of the children in the control group received ketorolac in the PACU compared with 20% of the morphine group (P < 0.01). The incidence of emesis for the 24 h after arrival in the PACU was 56% for those who received morphine compared with 25% in the control group (P < 0.01). CONCLUSIONS: For children undergoing inguinal surgery, the administration of a single dose of intravenous morphine after the induction of anesthesia smooths emergence from anesthesia as assessed by improved cooperation and sedation in the PACU, decreases the need for postoperative analgesics, but increases the incidence of vomiting in the first 24 h after surgery.     

Ontogenic development of the adenylyl cyclase enzyme and the alpha s, alpha i1 and alpha i2 G-protein regulatory subunits from rat prostate

STUDY OBJECTIVE: To compare the prophylactic administration of ondansetron with droperidol or placebo to determine its effectiveness in reducing postoperative nausea and vomiting after middle ear procedures. DESIGN: Prospective, randomized, double-blind study. SETTING: Inpatient otolaryngology service at a university medical center. PATIENTS: 120 ASA physical status I and II patients presenting for elective middle ear surgical procedures. INTERVENTIONS: Patients were randomly assigned to receive either placebo (Group 1), ondansetron 4 mg intravenously (IV) (Group 2), or droperidol 25 mcg/kg i.v. (Group 3) 10 minutes before induction of general anesthesia using thiopental 5 mg/kg i.v. with fentanyl 2 mcg/kg i.v. and maintenance anesthesia with isoflurane 1% to 2% end-tidal in a 50% air/oxygen mixture. MEASUREMENTS AND MAIN RESULTS: Total surgical, anesthesia, extubation, and postanesthesia care unit (PACU) occupancy times were recorded along with anesthesia recovery scores. The incidence and severity of nausea, vomiting, and pain along with rescue antiemetic administration, also were recorded. Similar assessments were made over the next 24 hours. Intergroup demographic data were similar except that the male to female ratio was higher in the ondansetron group. Stewart scores, reflecting emergence from anesthesia, were higher with ondansetron compared with droperidol. The incidence of nausea was similar between the groups but the severity was less after ondansetron therapy. More patients vomited after placebo than when given either droperidol or ondansetron. No intergroup differences were noted in the use of rescue antiemetics. Twenty-four hours later, more patients who received the placebo drug had nausea or vomited compared with either ondansetron or droperidol. CONCLUSIONS: Ondansetron 4 mg i.v. is as effective as droperidol and better than placebo in preventing nausea and vomiting in patients undergoing middle ear surgery. No cost advantage as determined by lower use of rescue antiemetics or shorter PACU times was noted after the prophylactic administration of ondansetron.     

Local wound infiltration with bupivacaine in lumbar laminectomy

BACKGROUND: Parenteral administration of narcotics has been the mainstay for postoperative pain relief in patients undergoing lumbar laminectomy. However, this may lead to respiratory depression and nausea, which may be hazardous in these patients. METHODS: We evaluated the efficacy of wound infiltration with bupivacaine in 45 consecutive patients undergoing elective single-level lumbar laminectomy for intervertebral disc prolapse in a prospective, double-blind, randomized controlled trial. Prior to wound closure, the muscle and subcutaneous tissues were infiltrated with bupivacaine 0.375% or sterile physiologic saline. Postoperatively, the patients were assessed hourly for pain and an analgesic administered if the patient had moderate or severe pain. RESULTS: All the 21 placebo recipients required analgesics in the first 9 hours postoperatively, compared to only 11 of 24 patients who received bupivacaine (p < 0.001). The mean (standard deviation) time before administration of the first dose of analgesic postoperatively in the bupivacaine and placebo recipients was 807.7 (567.6) minutes and 181.4 (110.1) minutes, respectively (p < 0.001). No adverse effects of local wound infiltration were noted. CONCLUSIONS: Local wound infiltration with bupivacaine is a safe and effective method for providing postoperative pain relief and reducing narcotic use in patients undergoing lumbar laminectomy.     

Evaluation of the synergism between ketorolac and morphine in the treatment of postoperative pain

BACKGROUND: The aim of the study is to determine what concentration of ketorolac and morphine administered together i.v. achieve best synergic effect between NSAID antiinflammatory and opioids analgesic properties. DESIGN: Randomized comparative study was carried out on 180 patients, ASA II-IV, undergoing major general surgery, in an University Clinic. METHODS: Postoperative pain therapy by i.v. PCA: group 1 morphine 0.75 mg.ml + ketorolac 0.75 mg.ml; group 2 morphine 0.50 mg.ml + ketorolac 1.50 mg.ml; group 3 morphine 0.25 mg.ml + ketorolac 1.50 mg.ml; in saline solution. Initial bolus: 2 ml. Continuous infusion 1.5 ml.h. Demand bolus: 0.2 ml. Lockout time: 30 minutes. Evaluations included: pain intensity (T0, T3, T18); total amount of infused drugs (T18); number of valid demands and attempts (T18); amount of autoadministered analgesic drugs in percent of highest available amount (T18); side effects (T18); patient's judgment. DATA ANALYSIS: ANOVA and Student's "t"-test. RESULTS: A statistically significant reduction of pain intensity was found after 3 and 18 hours in the three groups, no differences were found among the groups. Group 2 required an amount of autoadministered drugs significantly lower than other groups. Rare side effects. Patient's judgment was generally positive. CONCLUSIONS: Results suggest a greater synergetic effect between morphine and ketorolac in concentrations used in group 2.     

A mammographic evaluation of the morphostructural variations of the breast during hormone-replacement therapy in the postmenopause

OBJECTIVE: To compare i.v. ketorolac with i.v. prochlorperazine as the initial treatment of migraine headaches in the ED. METHODS: A prospective, double-blind comparison study was performed, using a convenience sample of 64 patients suffering from migraine headaches presenting to the ED at a tertiary care university teaching hospital. Patients were randomly assigned to receive either 10 mg of prochlorperazine i.v. or 30 mg of ketorolac i.v.. Patients scored the severity of their headaches using a 10-cm visual analog pain scale. An initial mark was made on the scale at the time of entry into the study and later another mark was made on a new unmarked pain scale 1 hour after medication administration. Changes in pain scores within each treatment group and between groups were analyzed using the Wilcoxon rank sum test. RESULTS: Prior to treatment, the patients assigned to receive prochlorperazine had a median score of 9.2 cm (mean +/- SD pain score of 8.3 cm +/- 2.1 cm), while the patients receiving ketorolac had a median score of 9.0 (mean pain score of 8.4 cm +/- 1.7 cm). There was no significant difference between the pain scores of the participants in the 2 groups prior to treatment (p = 0.80). One hour after medication administration, the patients in the prochlorperazine group had a median score of 0.5 cm (mean 2.1 +/- 3.2 cm), while those patients receiving ketorolac had a median pain score of 3.9 (mean 4.0 +/- 3.3 cm). The decrease in pain score was significant for both groups of patients (p = 0.0001). The change in pain score for the patients in the prochlorperazine group (median 7.1) was significantly greater than the change in pain score for the patients in the ketorolac group (median 4.0; p = 0.04). CONCLUSION: Although both drugs were associated with a significant reduction in pain scores, benefit over a placebo agent was not tested. Furthermore, the patients who received prochlorperazine i.v. for migraine headaches had a statistically significant greater decrease in their pain scores than did those receiving ketorolac i.v.     

Destruction of the auditory thalamus disrupts the production of fear but not the inhibition of fear conditioned to an auditory stimulus

Although ondansetron (4 mg I.V.) is effective in the prevention and treatment of postoperative nausea and vomiting (PONV) after ambulatory surgery, the optimal timing of its administration, the cost-effectiveness, the cost-benefits, and the effect on the patient's quality of life after discharge have not been established. In this placebo-controlled, double-blind study, 164 healthy women undergoing outpatient gynecological laparoscopic procedures with a standardized anesthetic were randomized to receive placebo (Group A), ondansetron 2 mg at the start of and 2 mg after surgery (Group B), ondansetron 4 mg before induction (Group C), or ondansetron 4 mg after surgery (Group D). The effects of these regimens on the incidence, severity, and costs associated with PONV and discharge characteristics were determined, along with the patient's willingness to pay for antiemetics. Compared with ondansetron given before induction of anesthesia, the administration of ondansetron after surgery was associated with lower nausea scores, earlier intake of normal food, decreased incidence of frequent emesis (more than two episodes), and increased times until 25% of patients failed prophylactic antiemetic therapy (i.e., had an emetic episode or received rescue antiemetics for severe nausea) during the first 24 h postoperatively. This prophylactic regimen was also associated with the highest patient satisfaction and lowest cost-effectiveness ratios. Compared with the placebo group, ondansetron administered after surgery significantly reduced the incidence of PONV in the postanesthesia care unit and during the 24-h follow-up period and facilitated the recovery process by reducing the time to oral intake, ambulation, discharge readiness, resuming regular fluid intake and a normal diet. When ondansetron was given as a "split dose," its prophylactic antiemetic efficacy was not significantly different from that of the placebo group. In conclusion, the prophylactic administration of ondansetron after surgery, rather than before induction, may be associated with increased patient benefits. Implications: Ondansetron 4 mg I.V. administered immediately before the end of surgery was the most efficacious in preventing postoperative nausea and vomiting, facilitating both early and late recovery, and improving patient satisfaction after outpatient laparoscopy.     

Intravenous dolasetron and ondansetron in prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study

BACKGROUND: Intravenous dolasetron mesilate has shown efficacy in the prevention of postoperative nausea and vomiting (PONV) when administered as a single dose prior to emergence from anesthesia. This trial compared intravenous dolasetron and ondansetron for the prevention of PONV when administered at induction of anesthesia. METHODS: This double-blind, placebo-controlled, multicenter trial randomized patients to one of four single IV treatments placebo, 25 or 50 mg dolasetron, or 4 mg ondansetron. Efficacy was measured by complete response (0 emetic episodes and no rescue medication), nausea severity and patient satisfaction as measured on a visual analog scale (VAS), investigator's rating, of nausea severity, and total response (complete response with no nausea [< or = 5 mm VAS]). RESULTS: 514 patients at 24 sites were evaluated for efficacy. The 50 mg dolasetron and 4 mg ondansetron doses were statistically equivalent, and superior to placebo, for all efficacy measures. Complete response rates were 49%, 51%, 71% and 64% for placebo, 25 and 50 mg dolasetron, and ondansetron, respectively. Dolasetron 50 mg was statistically superior to 25 mg dolasetron for complete response, total response, VAS maximum nausea, time to first emetic episode, and patient satisfaction. The majority of adverse events were of mild-to-moderate intensity. Headache was the most frequently reported treatment-related adverse event with a 3%-5% incidence across treatments. CONCLUSION: When given at induction of anesthesia, 50 mg intravenous dolasetron is equivalent to 4 mg ondansetron and superior to 25 mg dolasetron and placebo for the prevention of PONV. All treatments were safely administered and well tolerated.     

Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid

STUDY OBJECTIVE: To determine the efficacy of theophylline when given in addition to nebulized albuterol and intravenously administered corticosteroid to children hospitalized with mild to moderate asthma. DESIGN: Randomized, prospective, placebo-controlled, double-blind trial. SETTING: Tertiary-care children's hospital. PATIENTS: Twenty-nine patients with asthma between the ages of 2 and 16 years completed the study. The treatment and placebo groups were similar in age, gender, race, illness severity, and emergency department treatment. INTERVENTIONS: All patients received intravenously administered methylprednisolone and nebulized albuterol. The treatment group received intravenous theophylline therapy and the placebo group dextrose in water. When intravenously administered medications were discontinued, therapy continued with oral administration of theophylline (or placebo) and of prednisone. MEASUREMENTS AND MAIN RESULTS: Twice-daily assessments of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate, inspiratory/expiratory ratio, wheeze, and accessory muscle use. Time required to reach study discharge criteria (asthma score < or = 2) (30.4 +/- 16.8 vs 27.0 +/- 10.3 hours; p = 0.51) and the rate of improvement of the clinical asthma score (-0.10 +/- 0.05 unit/hr vs -0.11 +/- 0.09 unit/hr; p = 0.88) were not significantly different between the theophylline and placebo groups. The number of albuterol aerosol treatments required and the adverse effects experienced were not significantly different between groups. CONCLUSION: When the combination of systemically administered corticosteroid and inhaled albuterol is used in the treatment of children hospitalized with mild to moderate asthma, addition of theophylline may not be justified.     

Postoperative analgesia in herniated disk surgery. Comparative study of diclofenac , lysine acetylsalicylate, and ketorolac

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating musculoskeletal pain and are theoretically ideal for treating postoperative pain of the lumbar column. OBJECTIVES: To compare the analgesic efficacy and side effects of treatment with 3 NSAIDs (lysine acetylsalicylate, ketorolac and diclofenac) in the treatment of pain after surgery for lumbar disc hernia. PATIENTS AND METHODS: We enrolled 75 ASA I-II patients undergoing discectomy because of lumbar disc hernia; balanced general anesthesia was used in all cases. The patients were randomly distributed in 3 groups based on type of analgesia given in the immediate postoperative period. Group A received lysine acetylsalicylate (1800 mg), group B received ketorolac (30 mg) and group C received diclofenac (75 mg). The analgesics were diluted in 100 mg of saline solution and administered through a peripheral vein over 10 min. We evaluated the analgesia attained on a visual analog scale (VAS) and the physiological response to pain was assessed by monitoring changes in arterial pressure, heart rate and breathing frequency. If analgesia was insufficient 30 min after administration of the drug, 200 mg of lysine cloximate was given as a top-up. The side effects of each drug were also recorded. RESULTS: VAS evaluation showed significant reductions in pain 60 min after administration in groups A and B and after 120 min in group C. Nine patients in each group required lysine cloximate. There were no significant differences in physiological response among the 3 groups. No patient suffered major side effects. Mild side effects were reported most often in group B. CONCLUSIONS: The NSAIDs studied were inadequately for treating pain after surgery for lumbar disc hernia. Ketorolac was no better than the other analgesics studied but was associated with a higher number of mild side effects.     

Restricted expression of Fc gammaRIII (CD16) in synovium and dermis: implications for tissue targeting in rheumatoid arthritis (RA)

The authors conducted a prospective randomised double-blind comparison of patient-controlled analgesia (PCA), with a combination of morphine and ketorolac versus morphine alone and ketorolac alone in the management of postoperative pain after orthopaedic surgery. Forty-two patients were randomly assigned to three groups. Group 1 was given 1 mg/ml morphine, group 2 was given 3 mg/ml ketorolac and group 3 half-doses of each. After a loading dose of 0.07 ml/kg, PCA was started at an initial setting of 1 ml per demand, with a 10-min lock-out interval and no background infusion. Pain was measured at rest and during movements for 48 h. The combination of morphine and ketorolac was more effective than morphine or ketorolac alone in relieving rest pain throughout the study. The combination was also more effective during movement than either drug alone, but only for the first 24 h. The consumption of morphine and ketorolac was significantly lower when the two drugs were administered together. The incidence of urinary retention was highest in the group given morphine alone. The combination of half-doses of morphine and ketorolac is more effective in controlling postoperative pain than either drug alone. This combination also reduces analgesic consumption and morphine-related adverse events.     

Efficacy of ondansetron and prochlorperazine for the prevention of postoperative nausea and vomiting after total hip replacement or total knee replacement procedures: a randomized, double-blind, comparative trial

BACKGROUND: Limited data are available on the efficacy of ondansetron hydrochloride compared with prochlorperazine maleate for the treatment of postoperative nausea and vomiting (PONV). OBJECTIVE: To evaluate the comparative efficacy of ondansetron and prochlorperazine for the prophylaxis of PONV in patients undergoing total hip replacement or total knee replacement procedures. METHODS: A randomized, double-blind, comparative trial was conducted at a tertiary care, university hospital. Seventy-eight patients undergoing elective total hip or total knee replacement procedures received a single dose of ondansetron hydrochloride (n = 37), 4 mg intravenously, or prochlorperazine maleate (n = 41), 10 mg intramuscularly, at the end of the surgical procedure. Rescue therapy was administered every 4 hours as needed during the initial 48 hours. Primary outcome measures were the incidences and severity of PONV. Secondary outcome measures included the number of rescue antiemetic doses required, number of physical therapy cancellations because of PONV, length of hospital stay, and cost of antiemetic agents administered. RESULTS: The incidence of nausea was significantly greater in the ondansetron group compared with the prochlorperazine group (81% vs 56%; odds ratio, 3.4; 95% confidence interval, 1.2-9.4) as was the severity of nausea (P = .04). Multivariate analysis identified administration of ondansetron, history of PONV, obesity, and female sex as risk factors for a nausea event. The incidence of vomiting tended to be greater in the ondansetron group (49% vs 32%; odds ratio, 2.0; 95% confidence interval, 0.8-5.0). The need for rescue antiemetic therapy was also greater in the ondansetron group (46% vs 27%; odds ratio, 2.3; 95% confidence interval, 0.9-6.0). The mean antiemetic drug cost per patient was significantly greater for the ondansetron group ($47.56 vs $2.47; P<.001). However, the proportion of patients who were unable to participate in physical therapy because of PONV and the median length of hospital stay were similar in both groups. CONCLUSION: Prochlorperazine is associated with superior efficacy and significant cost savings compared with ondansetron for the prevention of PONV in patients undergoing total hip and total knee replacement procedures.     

The efficacy of RS-25259, a long-acting selective 5-HT3 receptor antagonist, for preventing postoperative nausea and vomiting after hysterectomy procedures

We evaluated the safety and efficacy of RS-25259, a potent and long-acting selective 5-HT3 receptor antagonist, for the prevention of postoperative nausea and vomiting (PONV) in women undergoing hysterectomy procedures. In this randomized, double-blind, placebo controlled, dose-ranging study, 218 healthy, consenting women were assigned to one of the six treatment groups: placebo or RS-25259 0.1, 0.3, 1.0, 3.0, or 30 microg/kg. All patients underwent a standardized general anesthetic technique. The study medication was administered i.v. 20-30 min before the end of surgery. During the initial 24-h period after surgery, the incidence of vomiting, the need for rescue antiemetics, the time to the first episode of emesis, and administration of rescue antiemetic medication, as well as a nausea visual analog scale and verbal categorical scale scores were recorded. In addition, recovery times from the end of anesthesia and the incidences of perioperative side effects were noted. Only 30 microg/kg RS-25259 significantly decreased the incidence of vomiting and the requirement for rescue antiemetics. The largest dose of RS-25259 also delayed the time to the first emetic episode and reduced the number of treatment failures. However, no differences were found in the severity of postoperative nausea (versus saline), and postoperative headaches were more common after the administration of RS-25259 0.3-30 microg/kg i.v. In conclusion, RS-25259 30 microg/kg i.v. was effective in reducing the incidence of PONV after major gynecologic surgery, but the occurrence of headaches with the larger doses of RS-25259 is a concern. Implications: RS-25259, a long-acting 5-HT3 antagonist, was effective in reducing postoperative vomiting only at the largest dose studied (30 microg/kg). However, RS-25259 had no antinausea activity, and the larger doses were associated with an increased incidence of headaches in the postoperative period.     

Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo

PURPOSE: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.