Fewer adverse effects associated with a modified two-bag intravenous acetylcysteine protocol compared to traditional three-bag regimen in paracetamol overdose.

Context: The intravenous (IV) N-acetylcysteine (NAC) regimen used worldwide in paracetamol overdose is complex with three separate weight-based doses and is associated with a high incidence of adverse events including non-allergic anaphylactoid reactions (NAARs). In 2012, Denmark adopted the two-bag IV NAC regimen which combined the first two infusions of the three-bag regimen and kept the third infusion unchanged. We compared the safety and efficacy of the two-bag IV NAC regimen with the traditional Danish three-bag regimen. Methods: A medical chart review was conducted in three Danish medical centers from January 2012 through December 2014. Safety and efficacy data were compared for patients who received the traditional infusion protocol in Denmark or the 20-h two-bag IV regimen. Results: Four hundred and ninety-three cases received the two-bag regimen and 274 received the three-bag regimen. The overall incidence of NAARs was 9% with all being mild to moderate in intensity. Fewer subjects in the two-bag group (4%) developed NAARs compared to 17% in the three-bag group (p < .001). Overall, 31 patients (4%) developed hepatotoxicity. There was no apparent difference in hepatotoxicity rates between the groups and no deaths or liver transplants. Patients receiving the two-bag regimen had fewer interruptions or delays (5%) compared to the three-bag regimen cohort (12%). Overall, there were very few medication errors reported (1%). Conclusions: The incidence of NAARs was lower in patients receiving acetylcysteine in a two-bag regimen compared to the traditional Danish three-bag regimen without an apparent reduction in efficacy.

A multicenter, randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (i.v.-ibuprofen) in the management of postoperative pain following abdominal hysterectomy.

BACKGROUND: Ibuprofen and other nonsteroidal anti-inflammatory drugs are widely used to block pain and inflammation in a variety of settings. Contrarily, opioid analgesia does not block the inflammatory component of pain and the use of these agents can be accompanied by serious side effects. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of intravenous ibuprofen (i.v.-ibuprofen) as a postoperative analgesic. METHODS: A total of 319 patients were randomly assigned in a 1:1 ratio to receive 800 i.v.-ibuprofen or placebo every 6 hours; in addition patients had access to morphine at a dose of 1-2 mg every 5 minutes. The primary outcome measure was median morphine consumption within the first 24 hours following surgery. RESULTS: During the first 24 hours of treatment, the median morphine requirement was reduced by 19% (P ≤ 0.001) and resulted in a significant reduction in pain at rest (AUC, 6 to 24 hours and 12 to 24 hours, P < 0.001) and pain with movement (AUC, 6 to 24 hours, P = 0.010 and 12 to 24 hours, P ≤ 0.001) as measured by the visual analog scale (VAS) in patients receiving 800 mg i.v.-ibuprofen compared to placebo. Time to ambulation was significantly faster (P = 0.018) in the i.v.-ibuprofen treated group, as well. Similar treatment-emergent adverse events occurred across both study groups and there was no difference in the overall incidence of these events. CONCLUSION: This study demonstrated that i.v.-ibuprofen is an effective analgesic medication that is safe and well tolerated when administered as an 800 mg dose every 6 hours in patients undergoing total abdominal hysterectomy surgery.

A multi-center, randomized, double-blind placebo-controlled trial of intravenous-ibuprofen (IV-ibuprofen) for treatment of pain in post-operative orthopedic adult patients.

OBJECTIVE: To determine whether pre- and post-operative administration of intravenous ibuprofen (IV-ibuprofen) can significantly decrease pain and morphine use when compared with placebo in adult orthopedic surgical patients. DESIGN: This was a multi-center, randomized, double-blind placebo-controlled trial. SETTING: This study was completed at eight hospitals; six in the United States and two in South Africa. PATIENTS: A total of 185 adult patients undergoing elective orthopedic surgery. INTERVENTIONS: Patients were randomized to receive either 800 mg IV-ibuprofen or placebo every 6 hours, with the first dose administered pre-operatively. Additionally, all patients had access to intravenous morphine for rescue. OUTCOME MEASURES: Efficacy of IV-ibuprofen was demonstrated by measuring the patient's self assessment of pain using a visual analog scale (VAS; assessed with movement and at rest) and a verbal response scale (VRS). Morphine consumption during the post-operative period was also assessed. RESULTS: In the immediate post-operative period, there was a 25.8% reduction in mean area under the curve-VAS assessed with movement (AUC-VASM) in patients receiving IV-ibuprofen (P < 0.001); a 31.8% reduction in mean AUC-VAS assessed at rest (AUC-VASR; P < 0.001) and a 20.2% reduction in mean VRS (P < 0.001) compared to those receiving placebo. Patients receiving IV-ibuprofen used 30.9% less morphine (P < 0.001) compared to those receiving placebo. Similar treatment emergent adverse events occurred in both study groups and there were no significant differences in the incidence of serious adverse events. CONCLUSION: Pre- and post-operative administration of IV-ibuprofen significantly reduced both pain and morphine use in orthopedic surgery patients in this prospective randomized placebo-controlled trial.

A multicenter, randomized, double-blind, placebo-controlled trial of intravenous ibuprofen 400 and 800 mg every 6 hours in the management of postoperative pain.

BACKGROUND: Although opioids are the mainstay of inpatient postoperative pain management, they do not block inflammation. The NSAID ibuprofen has antiinflammatory and analgesic properties, and a multimodal approach may reduce opioid requirements. OBJECTIVE: This study was conducted to assess the effects of intravenously administered ibuprofen 400 and 800 mg q6h in postoperative pain management. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial was conducted in 406 patients scheduled to undergo elective, single-site orthopedic or abdominal surgery. All patients received morphine administered by patient-controlled analgesia pump, or by hospital staff at the request of the patient, after surgery and were randomly assigned in a 1:1:1 ratio to receive ibuprofen 400 mg IV, ibuprofen 800 mg IV, or inactive vehicle (placebo). The first dose of study drug was administered intraoperatively at the initiation of wound closure, then every 6 hours for a total of 8 doses over the first 48 hours of the study. After the initial 8 doses, the protocol allowed for continued administration of IV ibuprofen or placebo every 6 hours, at the discretion of the investigator, for control of postoperative pain for a total of up to 120 hours (5 days). The ibuprofen and placebo were administered while patients had access to morphine throughout the duration of the study. The primary outcome measure was morphine use in the first 24 hours after surgery. Secondary measures were patient self-reports of pain scores at rest and with movement. Pain intensity was measured before (baseline) and at 1, 2, 3, 6, 9, 12, 15, 18, 24, 27, 30, 33, 36, 39, 42, 45, and 48 hours after the first administration of study medication, and then once daily through day 5 if the patient continued to receive study medication. Patients were assessed by study personnel for treatment-emergent adverse events (AEs). RESULTS: A total of 406 patients were enrolled (319 women, 87 men; mean [SD] age, 45 [12] years; weight, 83.8 [19.1] kg; ibuprofen 400 mg IV, 134 patients; ibuprofen 800 mg IV, 138; and placebo, 134). In the intent-to-treat population, median morphine use was significantly reduced during the first 24 hours after administration of the study drug in patients who received ibuprofen 800 mg IV q6h (by 22% vs placebo; P = 0.030). The use of ibuprofen 800 mg IV q6h was associated with significant reductions in pain at rest and with movement across 3 time periods (1-24, 6-24, 12- 24 hours) compared with placebo. Ibuprofen 400 mg IV q6h was associated with significant reductions in pain at rest and with movement during the 6- to 24-hour and 12- to 24-hour time periods compared with placebo. The prevalences of AEs and abnormalities in laboratory measurements were not significantly different between patients who received IV ibuprofen and those who received placebo. Treatment-emergent AEs were reported in 368 of 406 patients (91%). With respect to the number of patients who experienced serious AEs, the differences in the 400-mg IV ibuprofen group (118/134 [88%]) and the 800-mg IV ibuprofen group (124/138 [90%]) compared with the placebo group (126/134 [94%]) were not statistically significant. There were significant reductions in the proportions of patients who experienced gastrointestinal disorders in the 400- and 800-mg IV ibuprofen groups compared with the placebo group (99/134 [74%] and 98/138 [71%], respectively, vs 113/134 [84%]; P = 0.05 and P = 0.009). There were significant reductions in the numbers of patients experiencing pyrexia in the 400- and 800-mg IV ibuprofen groups compared with the placebo group (9/134 [7%] and 10/138 [7%] vs 23/134 [17%]; P = 0.013 and P = 0.015). Dizziness occurred in a significantly greater proportion of patients in the ibuprofen 800-mg q6h group compared with the placebo group (P = 0.011). CONCLUSIONS: In these patients undergoing postoperative pain management, ibuprofen 800 mg IV q6h was associated with significant reductions in morphine use and pain at rest and with movement compared with placebo. Ibuprofen IV was not associated with significant increases in AEs compared with placebo, with the exception of dizziness with the 800-mg dose. These findings suggest that ibuprofen 800 mg IV q6h was effective for postoperative pain management and was generally well tolerated. ClinicalTrials.gov identifier: NCT00225732.