Effects of Liraglutide on Myocardial Function After Cardiac Surgery: A Secondary Analysis of the Randomised Controlled GLOBE Trial.

INTRODUCTION: Previous studies demonstrated the cardioprotective properties of glucagon-like peptide-1 receptor agonists in patients with diabetes or cardiac disease. We investigated whether preoperative subcutaneous liraglutide improves myocardial function after cardiac surgery. METHODS: We performed a pre-planned secondary analysis of adult patients undergoing cardiac surgery included in the GLOBE trial. Patients were randomised to receive 0.6 mg subcutaneous liraglutide on the evening before surgery and 1.2 mg after induction of anaesthesia, or matching placebo. Perioperative echocardiographic assessments, haemodynamic parameters, doses of vasoactive inotropic support and postoperative measurements of troponin, Creatine Kinase-MB , creatinine and lactate were compared between groups. RESULTS: The study population consisted of the entire intention-to-treat cohort of the GLOBE trial. In this study, 129 patients received liraglutide and 132 patients placebo. Baseline characteristics were comparable between groups. Postoperatively, 170 (65%) patients underwent echocardiography. In the liraglutide group, more patients had a normal left ventricular systolic function (68%, 59 patients) compared to placebo (53%, 44 patients), difference = 15%, 95%CI = 0-30, p = 0.049. Assessment of the right ventricle revealed no difference in function. CONCLUSIONS: Patients receiving short-term preoperative liraglutide treatment better maintained normal myocardial function after cardiac surgery. This study warrants further evaluation of the potential beneficial effects of GLP-1 receptor agonists in cardiac surgery patients.

Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients: a multicentre randomized superiority trial.

AIMS: Most cardiac surgery patients, with or without diabetes, develop perioperative hyperglycaemia, for which intravenous insulin is the only therapeutic option. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesized that preoperative administration of the glucagon-like peptide-1 receptor agonist liraglutide reduces the number of patients requiring insulin for glycaemic control during cardiac surgery. MATERIALS AND METHODS: In this randomized, blinded, placebo-controlled, parallel-group, balanced (1:1), multicentre randomized, superiority trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomized to receive 0.6 mg subcutaneous liraglutide on the evening before surgery and 1.2 mg after induction of anaesthesia or matching placebo. Blood glucose was measured hourly and controlled using an insulin-bolus algorithm. The primary outcome was insulin administration for blood glucose >8.0 mmol/L in the operating theatre. Research pharmacists used centralized, stratified, variable-block, randomization software. Patients, care providers and study personnel were blinded to treatment allocation. RESULTS: Between June 2017 and August 2018, 278 patients were randomized to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention-to-treat analyses (129 in the liraglutide group, 132 in the placebo group). In the liraglutide group, 55 (43%) patients required additional insulin compared with 80 (61%) in the placebo group and absolute difference 18% (95% confidence interval 5.9-30.0, P = 0.003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality or postoperative complications. CONCLUSIONS: Preoperative liraglutide, compared with placebo, reduces insulin requirements while improving perioperative glycaemic control during cardiac surgery.

Study protocol of the randomised placebo-controlled GLOBE trial: GLP-1 for bridging of hyperglycaemia during cardiac surgery.

INTRODUCTION: Perioperative hyperglycaemia is common during cardiac surgery and associated with postoperative complications. Although intensive insulin therapy for glycaemic control can reduce complications, it carries the risk of hypoglycaemia. GLP-1 therapy has the potential to lower glucose without causing hypoglycaemia. We hypothesise that preoperative liraglutide (a synthetic GLP-1 analogue) will reduce the number of patients requiring insulin to achieve glucose values<8 mmol l-1 in the intraoperative period. METHODS AND ANALYSIS: We designed a multi-centre randomised parallel placebo-controlled trial and aim to include 274 patients undergoing cardiac surgery, aged 18-80 years, with or without diabetes mellitus. Patients will receive 0.6 mg liraglutide or placebo on the evening before, and 1.2 mg liraglutide or placebo just prior to surgery. Blood glucose is measured hourly and controlled with an insulin bolus algorithm, with a glycaemic target between 4-8 mmol l-1. The primary outcome is the percentage of patients requiring insulin intraoperatively. ETHICS AND DISSEMINATION: This study protocol has been approved by the medical ethics committee of the Academic Medical Centre (AMC) in Amsterdam and by the Dutch competent authority. The study is investigator-initiated and the AMC, as sponsor, will remain owner of all data and have all publication rights. Results will be submitted for publication in a peer-reviewed international medical journal. TRIAL REGISTRATION NUMBER: NTR6323; Pre-results.

Correction: Validation of the Surgical Fear Questionnaire in Adult Patients Waiting for Elective Surgery.

[This corrects the article DOI: 10.1371/journal.pone.0100225.].

Validation of the surgical fear questionnaire in adult patients waiting for elective surgery.

OBJECTIVES: Because existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ. METHODS: Based on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (N = 3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis. RESULTS: EFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1-4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5-10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbach's alpha) was between 0.765-0.920 (SFQ-total), 0.766-0.877 (SFQ-s), and 0.628-0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity. DISCUSSION: The SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.