IMPORTANCE Multimodal postoperative analgesia is widely used but lacks evidence of benefit. OBJECTIVE Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens. DESIGN, SETTING, AND PARTICIPANTS Randomized, blinded, placebo-controlled, 4-group trial in 6Danishhospitalswith90-dayfollow-upthatincluded556patientsundergoingtotalhiparthroplasty (THA) from December 2015 to October 2017. Final date of follow-up was January 1, 2018. INTERVENTIONS Participants were randomized to receive paracetamol (acetaminophen) 1000 mg plus ibuprofen 400 mg (n = 136; PCM + IBU), paracetamol 1000 mg plus matched placebo (n = 142; PCM), ibuprofen 400 mg plus matched placebo (n = 141; IBU), or half-strength paracetamol 500 mg plus ibuprofen 200 mg (n = 140; HS-PCM + IBU) orally every 6 hours for 24 hours postoperatively, starting 1 hour before surgery. MAIN OUTCOMES AND MEASURES Two co-primary outcomes: 24-hour morphine consumption using patient-controlled analgesia in pairwise comparisons between the 4 groups (multiplicity-adjusted thresholds for statistical significance, P < .0042; minimal clinically important difference, 10 mg), and proportion of patients with 1 or more serious adverse events (SAEs) within 90 days (multiplicity-adjusted thresholds for statistical significance, P < .025). RESULTS Among 559 randomized participants (mean age, 67 years; 277 [50%] women), 556 (99.5%) completed the trial and were included in the analysis. Median 24-hour morphine consumption was 20 mg (99.6% CI, 0-148) in the PCM + IBU group, 36 mg (99.6% CI, 0-166) for PCM alone, 26 mg (99.6% CI, 2-139) for IBU alone, and 28 mg (99.6% CI, 2-145) for HS-PCM + IBU. The median difference in morphine consumption between the PCM + IBU group vs PCM alone was 16 mg (99.6% CI, 6.5 to 24; P < .001); for the PCM-alone group vs HS-PCM + IBU, 8 mg (99.6% CI, −1 to 14; P = .001); and for the PCM + IBU group vs IBU alone, 6 mg (99.6% CI, −2 to 16; P = .002). The difference in morphine consumption was not statistically significant for the PCM + IBU group vs HS-PCM + IBU (8 mg [99.6% CI, −2 to 16]; P = .005) or for the PCM-alone group vs IBU alone (10 mg [99.6% CI, −2 to 16]; P = .004) after adjustment for multiple comparisons and 2 co-primary outcomes. There was no significant difference between the IBU-alone group vs HS-PCM + IBU (2 mg [99.6% CI, −10 to 7]; P = .81). The proportion of patients with SAEs in groups receiving IBU was 15%, and in the PCM-alone group, was 11%. The relative risk of SAE was 1.44 (97.5% CI, 0.79 to 2.64; P = .18). CONCLUSIONS AND RELEVANCE Among patients undergoing THA, paracetamol plus ibuprofen significantly reduced morphine consumption compared with paracetamol alone in the first 24 hours after surgery; there was no statistically significant increase in SAEs in the pooled groups receiving ibuprofen alone vs with paracetamol alone. However, the combination did not result in a clinically important improvement over ibuprofen alone, suggesting that ibuprofen alone may be a reasonable option for early postoperative oral analgesia.

Background and objectives Freeze-dried plasma (FDP) has logistical advantages in terms of storage and reconstitution time compared to fresh-frozen plasma. In vitro studies show FDP to be equivalent to fresh-frozen plasma regarding coagulation and clotting capacities. FDP is used in an increasing number of countries. We wanted to evaluate the clinical effects of FDP in major haemorrhage compared to standard care.Methods MEDLINE, Embase, Central, Biosis Previews, WHO ICTRP, Clinical Trials and Open Grey were systematically searched from inception until September 2018, without language restriction. Studies were eligible if they examined haemorrhagic adult patients transfused with FDP. Our primary outcome was mortality. Two reviewers independently assessed studies for eligibility, extracted data and assessed bias.Results Nine studies were eligible for inclusion. Three studies had a comparison group: one was a randomized controlled trial and two were before and after comparisons. Six studies were uncontrolled. A total of 606 patients received FDP, while 72 patients received non-FDP transfusion. In total, five minor adverse effects were documented. Two studies compared FDP to fresh-frozen plasma and found no difference in 30-day mortality between the groups. The included studies were heterogenous and had several methodological weaknesses, such as no control group, missing data or no protocol. ConclusionsThe available research does not document the clinical effects of FDP. We cannot recommend or discourage use of FDP in major haemorrhage on base of available research.

Perioperative management of patients declining transfusions of blood products can be challenging both ethically and clinically. Jehovah's Witnesses (JW) decline treatment with blood products and have published a list of interventions they might accept as substitutes. No detailed documentation of available substitute interventions at Danish hospitals exists. Likewise, no national guidelines exist on how to optimise patients who refuse to receive treatment with blood products. The primary aim was to investigate which treatments are currently available to healthcare professionals in Denmark when treating patients who refuse transfusion of blood components. Additionally, we wanted to investigate how many departments have local guidelines for treatment for this group of patients. Based on our findings we would suggest potential improvements in the treatment of patients declining transfusion of blood components. Consultants from Danish departments of anaesthesiology, abdominal surgery and obstetrics were invited to participate in a nationwide cross‐sectional online survey. The questionnaire explored available interventions offered perioperatively. Respondents were all on‐call consultants. The questionnaire underwent content, face and technical validation during pilot testing. Ninety‐six of 108 (89%) respondents from 55 departments completed the questionnaire. Thirty‐five (36%) respondents reported having a departmental guideline mostly dealing with judicial aspects regarding patients declining transfusions with blood, and 34 (35%) would in collaboration with other professionals make an interdisciplinary strategy for patients declining transfusions with blood. For patients declining treatment with blood products in anticoagulant treatment, and hence with a greater risk of bleeding, reverting treatment is essential. Depending on the type of anticoagulant, between 31 (32%) and 59 (60%) of respondents reported locally available guidelines for reverting anticoagulant treatments. We found a considerable variation and limited availability of interventions to minimise blood loss in patients declining transfusion of blood components. This scarcity of local guidelines together with the considerable variation of available treatment documented in our survey could possibly be enhanced by a lack of national guidelines.