The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial.

BACKGROUND: Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. METHODS/DESIGN: 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. DISCUSSION: The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02885948 . Registered retrospectively on 4 July 2016. Protocol Version 2.0, 3 April 2017. Protocol identification (code or reference number): UCDCRC/15/006 EudraCT registration number: 2015-003504-22. Registered on 5 August 2015.

The effect of the suspension of the license for aprotinin on the care of patients undergoing cardiac surgery: a survey of cardiac anesthesiologists' and surgeons' opinions in the United Kingdom.

OBJECTIVE: The primary aim was to poll the opinions of cardiac anesthesiologists and surgeons as to the effect of the suspension of the license for aprotinin on patients undergoing cardiac surgery. DESIGN: A mailed questionnaire. SETTING: United Kingdom. PARTICIPANTS: Members of the Association of Cardiothoracic Anaesthetists and the Society for Cardiothoracic Surgery in Great Britain and Ireland with a UK address. INTERVENTIONS: A structured questionnaire. MEASUREMENTS AND MAIN RESULTS: Of the 546 dispatched surveys, 285 (52%) were returned. While the majority of respondents (61%) felt it had not had any effect, 29% of respondents felt the suspension of the license for aprotinin had had a detrimental effect on patient care and 2% an extremely detrimental effect. Eight percent of respondents reported a beneficial effect. Since license suspension, the reported use of aprotinin had declined and tranexamic acid use had risen. The majority of respondents reported no change in the use of packed red cells (66%), blood products (53%), mechanical cell salvage (84%), factor VIIa (79%), or frequency of reopening for bleeding (65%). Respectively, 32%, 45%, 24%, and 20% of respondents reported a perceived increased use of these products, and 30% reported an increased frequency of reopening for bleeding. Apart from knowledge regarding local aprotinin stock, there was no significant difference in opinions between surgeons and anesthesiologists. CONCLUSIONS: While the majority of respondents felt that the suspension of the license for aprotinin had no effect, almost a third felt it had impacted negatively on the care of patients undergoing cardiac surgery.