Continuous Glucose Monitoring and the Effect of Liraglutide in Cardiac Surgery Patients: A Substudy of the Randomized Controlled GLOBE Trial.

OBJECTIVES: The objectives of the current research were to evaluate the accuracy and reliability of continuous glucose monitoring (CGM) in patients undergoing cardiac surgery and assess the impact of preoperative liraglutide administration on perioperative glucose control as captured by CGM. DESIGN: This was a prospective, single-center, prespecified analysis of the GLOBE trial, a randomized controlled trial comparing preoperative liraglutide treatment to placebo in patients undergoing cardiac surgery. SETTING: The work took place at a single-center academic hospital in the Netherlands. PARTICIPANTS: Twenty-five patients undergoing cardiac surgery were recruited from the hospital's cardiac surgery department. INTERVENTIONS: Participants received the Dexcom G5 CGM system from the day before surgery until discharge from the intensive care unit after surgery. Additionally, participants were randomized to receive either preoperative liraglutide or placebo. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas (ABG) glucose measurements were collected as a reference and matched to CGM readings to assess accuracy and reliability. In 240 paired CGM-ABG glucose measurements, the mean absolute relative difference was 14.4 ± 12.5%. Temporary sensor interruption occurred mainly intraoperatively (92% of patients). The median duration of intraoperative sensor interruption was 65 (48-95) minutes. Liraglutide increased glycemic time in range 72% versus 47% in the control group (absolute difference 25%, 95% confidence interval -41.4 to -8.9, p = .004). CONCLUSIONS: Despite intraoperative sensor interruption, CGM seems an accurate method for semi-invasive, real-time assessment of blood glucose levels. CGM can provide a detailed observation of the pre- and postoperative glycemic trajectory, demonstrating increased time in range following perioperative liraglutide treatment compared with placebo.

Effects of sodium-glucose transporter-2 inhibition on systemic hemodynamics, renal function, and intra-renal oxygenation in sepsis-associated acute kidney injury.

BACKGROUND: People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI. METHODS: Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8). RESULTS: Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes. CONCLUSION: In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.

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.

Incidence, prevalence, and mortality of type 1 diabetes in children and youth in Burkina Faso 2013-2022.

AIM: There are no data on type 1 diabetes (T1D) incidence and prevalence in Burkina Faso. We aimed to determine these in persons aged <25 years (y) since the implementation of Life for a Child (LFAC) program in 2013. PATIENTS AND METHODS: Data were collected from the prospective program register. Diagnosis of T1D was clinical, based on presentation, abrupt onset of symptomatic hyperglycemia, need for insulin replacement therapy from diagnosis, and no suggestion of other diabetes types. RESULTS: We diagnosed 312 cases of T1D <25y in 2013-2022. Male-to-female ratio was 1:1. T1D incidence <25y per 100,000 population/year increased from 0.08 (CI 95% 0.07-0.60) in 2013 to 0.34 (CI 95% 0.26-0.45) in 2022 (p=0.002). Incidence <15y/y rose from 0.04 (CI 95% 0.01-0.10) to 0.27 (CI 95% 0.18-0.38) per 100,000/year in 2013 and 2022, respectively (p < 0.002). Prevalence per 100,000 population <25y was 0.27 (CI 95% 0.19-0.37) in 2013 and rose to 1.76 (CI 95% 1.546-1.99) in 2022 (p<0.0001). Mortality rate was 20 (CI 95% 13-29.6) per 1,000-person y. CONCLUSIONS: There is a low but sharply rising T1D incidence and prevalence rates in children and youth in Burkina Faso since LFAC program implementation. It is very likely this is partly due to improved case detection. Mortality remains substantial.

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.

Atrial fibrillation and survival on a medical intensive care unit.

BACKGROUND: Atrial fibrillation (AF) is common among patients in the intensive care unit (ICU) and can be triggered by severe illness or preexisting conditions. It is debated if AF is an independent predictor of poor outcome. METHODS: Data derives from a single center retrospective registry including all patients with a stay on the medical ICU for >24 h. The primary endpoint was ICU survival. Secondary endpoints included receiving mechanical support (renal, respiratory or circulatory), hemodynamic parameters during AF, rate and rhythm control strategies, anticoagulation, and documentation. RESULTS: A total of 616 patients (male gender 62.3%, median age 75 years) were included in our analysis. New-onset AF was diagnosed in 87 patients (14.1%), 136 (22.1%) presented with preexisting AF, and 393 (63.8%) did not develop AF. Initial episodes of new-onset AF exhibited higher hemodynamic instability than episodes in preexisting cases, with elevated heart rates and increased catecholamine doses (both p < 0.001). ICU survival in new-onset AF was 80.5% (70/87) compared to 92.4% (363/393) in patients without AF (OR 0.340, CI 0.182-0.658, p < 0.001). Likewise, ICU survival in preexisting AF was 86.8% (118/136) was significantly lower compared to no AF (OR 0.542, CI 0.290-0.986, p = 0.050*). Independent predictors of ICU survival for patients were atrial fibrillation (p = 0.016), resuscitation before or during ICU stay (p < 0.001), and receiving acute dialysis on ICU (p = 0.002). CONCLUSIONS: ICU survival is noticeably lower in patients with new-onset or preexisting atrial fibrillation compared to those without. Patients who develop new-onset AF during their ICU stay warrant special attention for both short-term and long-term care strategies.

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.

Superior Survival of Fully Cemented Fixation Compared to Hybrid Fixation in a Single Design Rotating Hinge Knee Implant.

BACKGROUND: Clinical observations revealed higher rates of aseptic loosening for hybrid fixated rotating hinge knee implants compared to fully cemented ones. We hypothesize that the use of a fully cemented fixation technique had a higher survival rate for aseptic loosening compared to a hybrid fixation technique in a rotating hinge knee implant. METHODS: All procedures of patients who were treated with the RT-PLUS rotating hinge knee implant (Smith & Nephew, Memphis, TN) between 2010 and 2018 were included. Primary outcome was revision for aseptic loosening. Kaplan-Meier survivorship and Cox proportional hazard regression analysis were performed to calculate survival rates and hazard ratios. RESULTS: A total of 275 hinge knee implants were placed in 269 patients (60 primary procedures, 215 revisions). Median follow-up was 7.3 ± 3.9 years. In total, 24 components (16 hybrid femur, 2 fully cemented femur, 6 hybrid tibia; all revision procedures) in 19 patients were revised for aseptic loosening. Kaplan-Meier survivorship analysis showed superior survival rates of fully cemented components (femur 97.1%; tibia 100%) compared to hybrid fixated components (femur 89.5%; tibia 95.9%) at the 10-year follow-up. Multivariate Cox hazard analysis showed a significantly higher risk of aseptic loosening for hybrid fixated components, a prior stemmed component and the femoral component. CONCLUSION: Fully cemented fixation showed superior survival rates for aseptic loosening compared to hybrid fixation in a single design rotating hinge knee implant. A prior stemmed component appears to be a risk factor for aseptic loosening and the femoral component seems to be more prone to loosening.