Intraoperative methadone for postoperative pain after laparoscopic hysterectomy: Protocol for a randomised, double-blind trial.

BACKGROUND: Hysterectomy is often carried out as same-day surgery. Treatment of postoperative pain is, therefore, of utmost importance to ensure timely discharge from hospital. Methadone has several desirable pharmacological features, including a long elimination half-life. Theoretically, a single intraoperative dose could provide long-lasting pain relief. METHODS: This is a single-centre, investigator-initiated, randomised, double-blind study. Two-hundred and fifty women, scheduled to undergo hysterectomy at Horsens Region Hospital, Denmark, are randomized to receive methadone (0.2 mg/kg) or morphine (0.2 mg/kg) intraoperatively, 60 minutes before extubation. Primary outcomes are opioid consumption at 6 and 24 hours. Secondary outcomes include pain intensity at rest and during coughing at 1, 3, 6, 24 and 48 hours; patient satisfaction at 3 and 24 hours, postoperative nausea and vomiting at 6, 24 and 72 hours, adverse events in the postanaesthesia care unit (PACU) and time until readiness for discharge. Another outcome is persistent abdominal pain after 4 months. CONCLUSIONS: The study outlined in this protocol will provide important information about the use of methadone in same-day hysterectomy patients. The results will presumably be applicable to other types of surgery involving visceral pain.

Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial.

Background: Laparoscopic hysterectomy is often carried out as day-stay surgery. Minimising postoperative pain is therefore of utmost importance to ensure timely discharge from hospital. Methadone has several desirable pharmacological features, including a long elimination half-life. Therefore, a single intraoperative dose could provide long-lasting pain relief. Methods: Patients scheduled to undergo laparoscopic hysterectomy were randomly allocated to receive methadone (0.2 mg kg-1) or morphine (0.2 mg kg-1) intraoperatively, 60 min before tracheal extubation. Primary outcomes were opioid consumption (oral morphine equivalents in milligrams) at 6 and 24 h. Secondary outcomes included pain intensity at rest and during coughing, patient satisfaction, postoperative nausea and vomiting, and adverse events up to 72 h after completion of surgery. Results: The postoperative median opioid consumption was reduced in the methadone group compared with the morphine group at 6 h (35.5 [0-61] mg vs 48 [31-74.5] mg; P=0.01) and 24 h (42 [10-67] mg vs 54.5 [31-83] mg; P=0.03). On arrival at the PACU, pain at rest was significantly lower in patients receiving methadone (numeric rating scale: 3 [2-5] vs 5 [3-6]), whereas pain scores at rest and coughing were not significantly different throughout the rest of the observation period. No differences in other secondary outcomes were found. Conclusions: In this randomised, blinded, controlled trial, opioid consumption was reduced during the first 24 postoperative hours in patients receiving methadone without causing an increase in adverse events. The difference observed might be considered as small and of limited clinical relevance. Clinical trial registration: NCT03908060; EudraCT no. 2018-004351-20.

Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial.

BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS/DESIGN: The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point. DISCUSSION: The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.

[Fewer indications for sedation in mechanical ventilation therapy]. / Færre indikationer for sedation ved respiratorbehandling.

Critically ill patients undergoing mechanical ventilation have traditionally been deeply sedated. In the latest decade growing evidence supports less sedation as being beneficial for the patients. A daily interruption of sedation has been shown to reduce the length of mechanical ventilation and the length of stay in the intensive care unit. Recently it has been shown that a strategy with no sedation of critically ill patients undergoing mechanical ventilation reduced the time patients received mechanical ventilation and reduced the length of both intensive care and hospital stay.