Risk of perioperative discontinuation of SGLT2 inhibitors.

When sodium-glucose cotransporter-2 (SGLT2) inhibitors were primarily prescribed for treatment of diabetes mellitus, guidelines recommended withholding SGLT2 inhibitors before surgery to mitigate the associated risk of ketoacidosis. However, currently, SGLT2 inhibitors are an established therapy for patients with heart failure, and there is evidence that withholding SGLT2 inhibitors can worsen these patients' cardiovascular risk profile. We present an updated risk-benefit analysis of withholding SGLT2 inhibitors before surgery, focusing on patients with heart failure and addressing the risk of ketoacidosis and its treatment in these patients. Clinicians should consider perioperative continuation of SGLT2 inhibitors when prescribed for treatment of heart failure.

Preoperative Glycosylated Haemoglobin Screening to Identify Older Adult Patients with Undiagnosed Diabetes Mellitus-A Retrospective Cohort Study.

More than 25% of older adults in Europe have diabetes mellitus. It is estimated that 45% of patients with diabetes are currently undiagnosed, which is a known risk factor for perioperative morbidity. We investigated whether routine HbA1c screening in older adult patients undergoing surgery would identify patients with undiagnosed diabetes. We included patients aged ≥65 years without a diagnosis of diabetes who visited the preoperative assessment clinic at the Amsterdam University Medical Center and underwent HbA1c screening within three months before surgery. Patients undergoing cardiac surgery were excluded. We assessed the prevalence of undiagnosed diabetes (defined as HbA1c ≥ 48 mmol·mol-1) and prediabetes (HbA1c 39-47 mmol·mol-1). Using a multivariate regression model, we analysed the ability of HbA1c to predict days alive and at home within 30 days after surgery. From January to December 2019, we screened 2015 patients ≥65 years at our clinic. Of these, 697 patients without a diagnosis of diabetes underwent HbA1c screening. The prevalence of undiagnosed diabetes and prediabetes was 3.7% (95%CI 2.5-5.4%) and 42.9% (95%CI 39.2-46.7%), respectively. Preoperative HbA1c was not associated with days alive and at home within 30 days after surgery. In conclusion, we identified a small number of patients with undiagnosed diabetes and a high prevalence of prediabetes based on preoperative HbA1c screening in a cohort of older adults undergoing non-cardiac surgery. The relevance of prediabetes in the perioperative setting is unclear. Screening for HbA1c in older adult patients undergoing non-cardiac surgery does not appear to help predict postoperative outcome.

Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration.

Prescriptions and use of glucagon-like peptide-1 (GLP-1) receptor agonists are increasing dramatically, as indications are expanding from the treatment of diabetes mellitus to weight loss for people with obesity. As GLP-1 receptor agonists delay gastric emptying, perioperative healthcare practitioners could be concerned about an increased risk for pulmonary aspiration during general anaesthesia. We summarise relevant medical literature and provide evidence-based recommendations for perioperative care for people taking GLP-1 receptor agonists. GLP-1 receptor agonists delay gastric emptying; however, ongoing treatment attenuates this effect. The risk of aspiration during general anaesthesia is unknown. However, we advise caution in patients who recently commenced on GLP-1 receptor agonists. After over 12 weeks of treatment, standard fasting times likely suffice to manage the risk of pulmonary aspiration for most otherwise low-risk patients.

Comparison of Postoperative Neurocognitive Function in Older Adult Patients with and without Diabetes Mellitus.

INTRODUCTION: Delayed neurocognitive recovery (DNR; neurocognitive disorder up to 30 days postoperative) and postoperative neurocognitive disorders (POCD; neurocognitive disorder 1-12 months postoperative) occur frequently after surgery, with diabetes mellitus (DM) suggested to contribute to this. This was a single-center prospective cohort study. The main aim of this study was to investigate the role of DM and preoperative hemoglobin A1c (HbA1c) in the development of POCDs after noncardiac surgery. METHODS: Older adult patients ≥65 years of age scheduled for elective surgery were recruited. The Modified Telephone Interview for Cognitive Status questionnaire (TICS-M), a test of global cognitive functioning, was administered to determine cognition. Preoperative, 30-day postoperative, and 6-month postoperative cognition were compared for patients with and without DM. Cognitive decline was subdivided into mild (1 to 2 standard deviations below controls) and major (≥2 standard deviations below controls) DNR or POCD. Preoperative HbA1c levels were correlated with TICS-M scores. RESULTS: We analyzed 102 patients [median (IQR [range]) age 72.0 (5 [68-74])]), who were divided into patients with DM (80 patients [78%]) and patients without DM (22 patients [22%]). Baseline cognitive function was similar for both groups. Repeated measures ANOVA showed that mean DM patient TICS-M scores decreased 30 days postoperative (F(2, 200) = 4.0, p = 0.02), with subsequent recovery 6-month postoperative, compared to stable TICS-M scores in non-DM patients. There were significantly more DM patients with DNR than non-DM patients (n = 11 [50%] vs. n = 14 [17.5%]; p = 0.031). There were no between-group differences in mild or major POCD. Higher preoperative HbA1c levels were significantly correlated with decreased 30-day Δcognition scores (F(1, 54) = 9.4, p = 0.003) with an R2 of 0.149 (ß -0.45, 95% confidence interval: -0.735 to -0.154). CONCLUSIONS: Older adult patients with DM undergoing surgery have an increased risk of DNR compared to older adult non-DM patients, but no increased risk of POCD. In DM patients, higher preoperative HbA1c levels were associated with an increased risk of DNR.

Type 1 and other types of diabetes mellitus in the perioperative period. What the anaesthetist should know.

Diabetes mellitus is often treated as a uniform disease in the perioperative period. Type 2 diabetes is most commonly encountered, and only a minority of surgical patients have been diagnosed with another type of diabetes. Patients with a specific type of diabetes can be particularly prone to perioperative glycaemic dysregulation. In addition, certain type-related features and pitfalls should be taken into account in the operating theatre. In this narrative review, we discuss characteristics of types of diabetes other than type 2 diabetes relevant to the anaesthetist, based on available literature and data from our clinic.

Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway.

AIMS/HYPOTHESIS: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations. METHODS: This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels. RESULTS: Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. CONCLUSIONS/INTERPRETATION: Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities.

Second Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management.

The COVID-19 pandemic poses great challenges for healthcare workers around the world, including perioperative specialists. Previously, we provided a first overview of available literature on SARS-CoV-2 and COVID-19, relevant for anaesthetists and intensivists. In the current review, we provide an update of this topic, after a literature search current through May 2020. We discuss the evidence on perioperative risk for COVID-19 patients presenting for surgery, the risk of transmission of SARS-CoV-2 in the operating room, and the current literature on laboratory diagnostics. Furthermore, cardiovascular and nervous system involvement in COVID-19 are discussed, as well as considerations in diabetic patients. Lastly, the latest evidence on pharmacological treatment is summarised.

Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management.

When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.

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.

Comparison of perioperative glucose regulation in patients with type 1 vs type 2 diabetes mellitus: A retrospective cross-sectional study.

BACKGROUND: Most perioperative diabetes mellitus (DM) guidelines do not distinguish between patients with type 1 (DM1) and type 2 (DM2). We hypothesised that similar treatment of DM1 and DM2 patients leads to differences in their perioperative glucose control. METHODS: We performed a retrospective cross-sectional study, of all DM patients undergoing surgery between May 2013 and November 2015 in a Dutch university hospital. We compared DM1 with DM2 patients, treated according to the same perioperative glucose protocol. Our primary outcome was the incidence of hyperglycaemia (glucose ≥10 mmol/L). Secondary outcomes were short-term glycaemic control (glucose before surgery and peak glucose perioperatively), long-term glycaemic control (HbA1c in 90 days before and after surgery) and the incidence of hypoglycaemia (glucose <4 mmol/L). RESULTS: We included 2259 patients with DM, 216 (10%) of which had DM1. The calculated incidences in our population were 7 out of 1000 patients with DM1 and 69 out of 1000 patients with DM2. Compared to those with DM2, patients with DM1 were younger, had a lower BMI, a higher glucose concentration before surgery, and a higher perioperative peak glucose concentration (11.0 [8.2-14.7] vs 9.4 [7.7-11.7], P < 0.001). The incidence of the primary endpoint, perioperative hyperglycaemia, was significantly higher in DM1 compared to DM2 patients (63% vs 43%, P < 0.001). Hypoglycaemia occurred more often in the DM1 population (7.1% vs 1.3%, P < 0.001). CONCLUSION: Providing similar perioperative treatment to patients with DM1 and DM2 is associated with poorer short-term and long-term glycaemic control in DM1 throughout the perioperative period as well as an increased risk of hypoglycaemia.

Systematic review of incretin therapy during peri-operative and intensive care.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are incretin hormones. By lowering blood glucose in a glucose-dependent manner, incretin-based therapies represent a novel and promising intervention to treat hyperglycaemia in hospital settings. We performed a systematic review of the literature for all current applications of incretin-based therapies in the peri-operative and critical care settings. METHODS: We searched MEDLINE, the Cochrane Library, and Embase databases for all randomised controlled trials using exogenous GLP-1, GLP-1 receptor agonists, exogenous GIP and dipeptidyl peptidase IV inhibitors in the setting of adult peri-operative care or intensive care. We defined no comparator treatment. Outcomes of interest included blood glucose, frequency of hypoglycaemia and insulin administration. RESULTS: Of the 1190 articles identified during the initial literature search, 38 fulfilled criteria for full-text review, and 19 single-centre studies were subsequently included in the qualitative review. Of the 18 studies reporting glycaemic control, improvement was reported in 15, defined as lower glucose concentrations in 12 and as reduced insulin administration (with similar glucose concentrations) in 3. Owing to heterogeneity, meta-analysis was possible only for the outcome of hypoglycaemia. This revealed an incidence of 7.4% in those receiving incretin-based therapies and 6.8% in comparator groups (P = 0.94). CONCLUSIONS: In small, single-centre studies, incretin-based therapies lowered blood glucose and reduced insulin administration without increasing the incidence of hypoglycaemia. TRIAL REGISTRATION: PROSPERO, CRD42017071926.

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.