Perioperative Fully Closed-loop versus Usual Care Glucose Management in Adults Undergoing Major Abdominal Surgery - A Two-centre Randomised Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of fully closed-loop (FCL) compared with usual care (UC) glucose control in patients experiencing major abdominal surgery-related stress hyperglycaemia. SUMMARY BACKGROUND DATA: Major abdominal surgery-related stress and periprocedural interventions predispose to perioperative hyperglycaemia, both in diabetes and non-diabetes patients. Insulin corrects hyperglycaemia effectively, but its safe use remains challenging. METHODS: In this two-centre randomised controlled trial, we contrasted subcutaneous FCL with UC glucose management in patients undergoing major abdominal surgery anticipated to experience prolonged hyperglycaemia. FCL (CamAPS HX, Dexcom G6, mylife YpsoPump 1.5x) or UC treatment was used from hospital admission to discharge (max 20 d). Glucose control was assessed using continuous glucose monitoring (masked in the UC group). The primary outcome was the proportion of time with sensor glucose values in target range 5.6-10.0 mmol/L. RESULTS: Thirty-seven surgical patients (54% pancreas, 22% liver, 19% upper gastrointestinal, 5% lower gastrointestinal), of whom 18 received FCL and 19 UC glucose management, were included in the analysis. Mean±SD percentage time with sensor glucose in target range was 80.1±10.0% in the FCL and 53.7±19.7% in the UC group (P<0.001). Mean±SD glucose was 7.5±0.5 mmol/L in the FCL and 9.1±2.4 mmol/L in the UC group (P=0.015). Time in hypoglycaemia (<3.0 mmol/L) was low in either group. No study-related serious adverse events occurred. CONCLUSIONS: The FCL approach resulted in significantly better glycaemic control compared to UC management, without increasing the risk of hypoglycaemia. Automated glucose-responsive insulin delivery is a safe and effective strategy to minimise hyperglycaemia in complex surgical populations.

Performance of the Dexcom G6 Continuous Glucose Monitoring System During Cardiac Surgery Using Hypothermic Extracorporeal Circulation.

OBJECTIVE: Continuous glucose monitoring (CGM) may be challenged by extreme conditions during cardiac surgery using hypothermic extracorporeal circulation (ECC). RESEARCH DESIGN AND METHODS: We evaluated the Dexcom G6 sensor in 16 subjects undergoing cardiac surgery with hypothermic ECC, of whom 11 received deep hypothermic circulatory arrest (DHCA). Arterial blood glucose, quantified by the Accu-Chek Inform II meter, served as reference. RESULTS: Intrasurgery mean absolute relative difference (MARD) of 256 paired CGM/reference values was 23.8%. MARD was 29.1% during ECC (154 pairs) and 41.6% immediately after DHCA (10 pairs), with a negative bias (signed relative difference: -13.7%, -26.6%, and -41.6%). During surgery, 86.3% pairs were in Clarke error grid zones A or B and 41.0% of sensor readings fulfilled the International Organization for Standardization (ISO) 15197:2013 norm. Postsurgery, MARD was 15.0%. CONCLUSIONS: Cardiac surgery using hypothermic ECC challenges the accuracy of the Dexcom G6 CGM although recovery appears to occur thereafter.

Fully Closed-Loop Insulin Delivery in Patients Undergoing Pancreatic Surgery.

The central role of pancreas in glucose regulation imposes high demands on perioperative glucose management in patients undergoing pancreatic surgery. In a post hoc subgroup analysis of a randomized controlled trial, we evaluated the perioperative use of subcutaneous (SC) fully closed-loop (FCL; CamAPS HX) versus usual care (UC) insulin therapy in patients undergoing partial or total pancreatic resection. Glucose control was compared using continuous glucose monitoring (CGM) metrics (% time with CGM values between 5.6 and 10.0 mmol/L and more). Over the time of hospitalization, FCL resulted in better glucose control than UC with more time spent in the target range 5.6-10.0 mmol/L (mean [standard deviation] % time in target 77.7% ± 4.6% and 41.1% ± 19.5% in FCL vs. UC subjects, respectively; mean difference 36.6% [95% confidence interval 18.5-54.8]), without increasing the risk of hypoglycemia. Findings suggest that an adaptive SC FCL approach effectively accommodated the highly variable insulin needs in patients undergoing pancreatic surgery. Clinical trials registration: ClinicalTrials.gov, NCT04361799.

Study protocol for a randomised, double-blind, placebo-controlled crossover trial assessing the impact of the SGLT2 inhibitor empagliflozin on postprandial hypoglycaemia after gastric bypass.

INTRODUCTION: Postprandial hypoglycaemia after gastric bypass surgery (also known as postbariatric hypoglycaemia or PBH) is an increasingly encountered clinical problem. PBH is characterised by meal-induced rapid spikes and consequent falls in glycaemia, resulting in both hypoglycaemia burden and high glycaemic variability. Despite its frequency, there is currently no approved pharmacotherapy. The purpose of this investigation is to evaluate efficacy and safety of empagliflozin 25 mg, a sodium-glucose cotransporter 2-inhibitor, to reduce glucose excursions and hypoglycaemia burden in patients with PBH after gastric bypass surgery. METHODS AND ANALYSIS: In a prospective, single-centre, randomised, double-blind, placebo-controlled, crossover trial, we plan to enrol 22 adults (≥18 years) with PBH after Roux-en-Y gastric bypass surgery (plasma or sensor glucose <3.0 mmol/L). Eligible patients will be randomised to receive empagliflozin 25 mg and placebo once daily, each for 20 days, in random order. Study periods will be separated by a 2-6 weeks wash-out period. The primary efficacy outcome will be the amplitude of plasma glucose excursion (peak to nadir) during a mixed meal tolerance test. Results will be presented as paired-differences±SD plus 95% CIs with p values and hypothesis testing for primary and secondary outcomes according to intention-to-treat. Secondary outcomes include continuous glucose monitoring-based outcomes, further metabolic measures and safety. ETHICS AND DISSEMINATION: The DEEP-EMPA trial (original protocol title: Randomized, double-blind, placebo-controlled crossover trialassessing the impact of the SGLT2 inhibitor empagliflozin onpostprandial hypoglycaemia after gastric bypass) was approved by the Bern Ethics Committee (ID 2021-01187) and Swissmedic (Ref. Number: 102663190) in October and November 2021, respectively. First results are expected in the first quarter of 2023 and will be disseminated via peer-reviewed publications and presented at national and international conferences. The acronym DEEP was derived from an overarching project title (DEciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia after Bariatric Surgery), the term EMPA stands for the drug empagliflozin. TRIAL REGISTRATION NUMBER: NCT05057819.

Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial.

OBJECTIVE: Perioperative management of glucose levels remains challenging. We aimed to assess whether fully closed-loop subcutaneous insulin delivery would improve glycemic control compared with standard insulin therapy in insulin-requiring patients undergoing elective surgery. RESEARCH DESIGN AND METHODS: We performed a single-center, open-label, randomized controlled trial. Patients with diabetes (other than type 1) undergoing elective surgery were recruited from various surgical units and randomly assigned using a minimization schedule (stratified by HbA1c and daily insulin dose) to fully closed-loop insulin delivery with fast-acting insulin aspart (closed-loop group) or standard insulin therapy according to local clinical practice (control group). Study treatment was administered from hospital admission to discharge (for a maximum of 20 days). The primary end point was the proportion of time with sensor glucose in the target range (5.6-10.0 mmol/L). RESULTS: Forty-five patients were enrolled and assigned to the closed-loop (n = 23) or the control (n = 22) group. One patient (closed-loop group) withdrew from the study before surgery and was not analyzed. Participants underwent abdominal (57%), vascular (23%), orthopedic (9%), neuro (9%), or thoracic (2%) surgery. The mean proportion of time that sensor glucose was in the target range was 76.7 ± 10.1% in the closed-loop and 54.7 ± 20.8% in the control group (mean difference 22.0 percentage points [95% CI 11.9; 32.0%]; P < 0.001). No episodes of severe hypoglycemia (<3.0 mmol/L) or hyperglycemia with ketonemia or any study-related adverse events occurred in either group. CONCLUSIONS: In the context of mixed elective surgery, the use of fully closed-loop subcutaneous insulin delivery improves glucose control without a higher risk of hypoglycemia.

Resolution of Precapillary Pulmonary Hypertension After Liver Transplantation for Hereditary Hemorrhagic Telangiectasia: Systematic Review and Case Report.

BACKGROUND: Pulmonary hypertension (PH) is a known complication of hereditary hemorrhagic telangiectasia (HHT) in patients with hepatic arteriovenous malformations (HAVM). Orthotopic liver transplantation (OLT) is a recognized treatment of HAVM in HHT, but its effect on PH has not been reported in detail before. METHODS: Systematic review on HHT patients with pre- or postcapillary PH who underwent OLT and report of a case. RESULTS: Twenty-one patients were included from 7 articles, all case reports or case series. All had high-output cardiac failure prior to OLT. Two patients had precapillary PH, both related to ALK1 mutations. All patients but 1 showed significant improvement or complete resolution of PH after transplantation. One patient died of acute cardiac failure postoperatively. We also report the case of a 72-year-old woman with type 3 HHT and severe mixed pre- and postcapillary PH. The patient presented with multiple HAVM, left-to-right shunting, and severe but partially reversible combined pre- and postcapillary PH, without ALK1 mutation. After recurrent cholangitis episodes, liver abscesses, and severe obstruction of the right-sided biliary tree, an interdisciplinary decision was taken to proceed with OLT despite PH. Intraoperatively, PH resolved almost instantly after hepatic artery ligation and hepatectomy. CONCLUSIONS: In our patient, OLT completely abrogated mixed pre- and postcapillary PH. Based on this systematic review, we suggest that OLT should be considered a viable treatment option in patients with HHT, HAVM, and mixed pre- and postcapillary PH, featuring cardiac failure and drug responsive PH, rather than being seen as a major risk factor for cardiopulmonary complications.

Assessment of Myocardial Function During Blood Pressure Manipulations Using Feature Tracking Cardiovascular Magnetic Resonance.

Background: Coronary autoregulation is a feedback system, which maintains near-constant myocardial blood flow over a range of mean arterial pressure (MAP). Yet in emergency or peri-operative situations, hypotensive or hypertensive episodes may quickly arise. It is not yet established how rapid blood pressure changes outside of the autoregulation zone (ARZ) impact left (LV) and right ventricular (RV) function. Using cardiovascular magnetic resonance (CMR) imaging, measurements of myocardial tissue oxygenation and ventricular systolic and diastolic function can comprehensively assess the heart throughout a range of changing blood pressures. Design and methods: In 10 anesthetized swine, MAP was varied in steps of 10-15 mmHg from 29 to 196 mmHg using phenylephrine and urapidil inside a 3-Tesla MRI scanner. At each MAP level, oxygenation-sensitive (OS) cine images along with arterial and coronary sinus blood gas samples were obtained and blood flow was measured from a surgically implanted flow probe on the left anterior descending coronary artery. Using CMR feature tracking-software, LV and RV circumferential systolic and diastolic strain parameters were measured from the myocardial oxygenation cines. Results: LV and RV peak strain are compromised both below the lower limit (LV: Δ1.2 ± 0.4%, RV: Δ4.4 ± 1.2%, p < 0.001) and above the upper limit (LV: Δ2.1 ± 0.4, RV: Δ5.4 ± 1.4, p < 0.001) of the ARZ in comparison to a baseline of 70 mmHg. LV strain demonstrates a non-linear relationship with invasive and non-invasive measures of oxygenation. Specifically for the LV at hypotensive levels below the ARZ, systolic dysfunction is related to myocardial deoxygenation (ß = -0.216, p = 0.036) in OS-CMR and both systolic and diastolic dysfunction are linked to reduced coronary blood flow (peak strain: ß = -0.028, p = 0.047, early diastolic strain rate: ß = 0.026, p = 0.002). These relationships were not observed at hypertensive levels. Conclusion: In an animal model, biventricular function is compromised outside the coronary autoregulatory zone. Dysfunction at pressures below the lower limit is likely caused by insufficient blood flow and tissue deoxygenation. Conversely, hypertension-induced systolic and diastolic dysfunction points to high afterload as a cause. These findings from an experimental model are translatable to the clinical peri-operative environment in which myocardial deformation may have the potential to guide blood pressure management, in particular at varying individual autoregulation thresholds.

Perioperative glucose management: Current status and future directions.

Hyperglycemia in surgical patients is common and associated with increased morbidity and mortality. Optimal perioperative care includes pre-surgery evaluation of glucose control, adequate preoperative management of glucose-lowering therapies, and repeated blood glucose monitoring on the day of surgery. There is consensus regarding the maintenance of intraoperative glucose levels below 10.0 mM through the use of subcutaneous or intravenous insulin, and over the avoidance of aggressive strategies in order to minimize the risk of hypoglycemia. As staffing levels are stretched and prevalence and complexity of cases increase, novel diabetes technologies such as continuous glucose monitoring, insulin pumps and closed-loop glucose control systems can potentially address unmet needs in the provision of perioperative diabetes care. This potential calls for well-designed clinical trials covering various aspects of perioperative glucose management in order to establish evidence-based and standardized practices. This long-term goal relies heavily on communication and collaboration in multidisciplinary teams that include anesthesiologists, surgeons, and endocrinologists.

Point-of-care ultrasound in the preoperative setting.

Point-of-care ultrasound (POCUS) is a widely used diagnostic tool, especially in emergency and critical care medicine, and it is increasingly being used in the perioperative setting. Its specific role in preoperative assessment of patients, however, has not yet been defined. While some data show innovative use of the technique in the preoperative setting, higher-level evidence to underscore potential advantages is still limited. We review and discuss a range of POCUS examinations which can potentially help anaesthesiologists in the preoperative clinic decide whether to perform additional testing, can assist in selecting the best anaesthetic approach, and can support perioperative and postoperative monitoring.

Impact of geography and surgical approach on recurrence in global pilonidal sinus disease.

Pilonidal sinus disease (PSD) is increasing globally. A recent meta-analysis and merged-data analysis showed that recurrence rates in PSD depend essentially on follow-up time and specific surgical procedures. However, the global distribution of surgical approaches and respective recurrence rates have never been studied in PSD. We aimed at studying the impact of geographic distribution of surgical approaches to treat PSD and subsequent geography-specific recurrence rates. We searched relevant databases as described previously. Recurrence rates were then associated with reported follow-up times and geographic origin. We simulated individual patients to enable analogy across data. Globally, recurrence rates range from 0.3% for Limberg/Dufourmentel approaches (95% CI 0.2-0.4) and flaps (95% CI 0.1-0.5) and up to 6.3% for incision (95% CI 3.2-9.3) at 12 months. Recurrence rates range from 0.3% for Karydakis/Bascom approaches (95% CI 0.0-0.8) up to 67.2% for incision (95% CI 7.5-100) in the USA, and 0.0% for primary asymmetric closure in Germany (95% CI 0.0-0.0). Our analysis shows that recurrence rates in PSD not only depend on therapeutic approaches and follow-up time but also on geography. Primary asymmetric closure and various flap techniques remain superior regardless of the geographical region. Some approaches have extraordinarily good outcomes in specific countries.

Implementation and Evaluation of a Web-Based Distribution System For Anesthesia Department Guidelines and Standard Operating Procedures: Qualitative Study and Content Analysis.

BACKGROUND: Digitization is spreading exponentially in medical care, with improved availability of electronic devices. Guidelines and standard operating procedures (SOPs) form an important part of daily clinical routine, and adherence is associated with improved outcomes. OBJECTIVE: This study aimed to evaluate a digital solution for the maintenance and distribution of SOPs and guidelines in 2 different anesthesiology departments in Switzerland. METHODS: A content management system (CMS), WordPress, was set up in 2 tertiary-level hospitals within 1 year: the Department of Anesthesiology and Pain Medicine at the Kantonsspital Lucerne in Lucerne, Switzerland, as an open-access system, followed by a similar system for internal usage in the Department of Anaesthesiology and Pain Medicine of the Inselspital, Bern University Hospital, in Bern, Switzerland. We analyzed the requirements and implementation processes needed to successfully set up these systems, and we evaluated the systems' impact by analyzing content and usage. RESULTS: The systems' generated exportable metadata, such as traffic and content. Analysis of the exported metadata showed that the Lucerne website had 269 pages managed by 44 users, with 88,124 visits per month (worldwide access possible), and the Bern website had 341 pages managed by 35 users, with 1765 visits per month (access only possible from within the institution). Creation of an open-access system resulted in third-party interest in the published guidelines and SOPs. The implementation process can be performed over the course of 1 year and setup and maintenance costs are low. CONCLUSIONS: A CMS, such as WordPress, is a suitable solution for distributing and managing guidelines and SOPs. Content is easily accessible and is accessed frequently. Metadata from the system allow live monitoring of usage and suggest that the system be accepted and appreciated by the users. In the future, Web-based solutions could be an important tool to handle guidelines and SOPs, but further studies are needed to assess the effect of these systems.

A Swiss nationwide survey shows that dual guidance is the preferred approach for peripheral nerve blocks.

Ultrasound has significantly increased safety and effectiveness in regional anesthesia. However, little is known about its clinical use. We studied clinical approaches currently used by anesthesiologists, conducted a nationwide survey, and analyzed data collected in ordered logistic regression models. All active members of the Swiss Society for Anaesthesiology and Resuscitation (SSAR/SGAR) were asked to participate. Reported practice in nerve localization, safety, and techniques used for peripheral nerve blocks (PNB) were main outcome measures. Experience ranged from 3 to >30 years. The mean number of block techniques mastered was 11.5 ± 5.9. Standard monitoring was regularly used, whereas sterile coats were less frequently used by anesthesiologists who self-estimated a higher level of expertise in PNB (ordered logit coefficient -0.05, 95% CI -0.07 to -0.02, P < 0.001; pseudo r2 = 0.019; probability > Chi2 = 0.02). The more self-estimated expertise anesthesiologists had, the less likely they were to use nerve stimulation in combination with ultrasound (dual guidance) (ordered logit coefficient -0.31; 95% CI -0.85 to -0.03: P = 0.03; pseudo r2 = 0.007; probability > Chi2 = 0.05). The high share of reported standard monitoring meets the recommendations of the Helsinki Patient Safety Declaration. Dual guidance appears to be the preferred approach for safely localizing nerves for PNB in Switzerland.

Relationship between myocardial oxygenation and blood pressure: Experimental validation using oxygenation-sensitive cardiovascular magnetic resonance.

BACKGROUND: The relationship between mean arterial pressure (MAP) and coronary blood flow is well described. There is autoregulation within a MAP range of 60 to 140 mmHg providing near constant coronary blood flow. Outside these limits flow becomes pressure-dependent. So far, response of myocardial oxygenation to changes in pressure and flow has been more difficult to assess. While established techniques mostly require invasive approaches, Oxygenation-Sensitive (OS) Cardiovascular Magnetic Resonance (CMR) is a technique that can non-invasively assess changes in myocardial tissue oxygenation. The purpose of this study was to follow myocardial oxygenation over a wide range of blood pressure variation within and outside known coronary autoregulatory limits using OS-CMR, and to relate these data to coronary hemodynamics. METHODS: Ten anaesthetized swine (German Large White) underwent left-sided thoracotomy and attachment of a perivascular flow probe to the proximal left anterior descending (LAD) coronary artery for continuous measurement of blood flow (QLAD). Thereafter, animals were transferred into a 3T MRI scanner. Mean arterial pressure (MAP) was varied in 10-15 mmHg steps by administering alpha1-receptor agents phenylephrine or urapidil. For each MAP level, OS-CMR images as well as arterial and coronary sinus blood gas samples were obtained simultaneously during brief periods of apnea. Relative changes (Δ) of coronary sinus oxygen saturation (ScsO2), oxygen delivery (DO2) and demand (MVO2), extraction ratio (O2ER) and excess (Ω) from respective reference levels at a MAP of 70 mmHg were determined and were compared to %change in OS-signal intensity (OS-SI) in simultaneously acquired OS-CMR images. RESULTS: QLAD response indicated autoregulation between MAP levels of 52 mmHg (lower limit) and127 mmHg (upper limit). OS-CMR revealed a global myocardial oxygenation deficit occurring below the lower autoregulation limit, with the nadir of OS-SI at -9.0%. With MAP values surpassing 70 mmHg, relative OS-SI increased to a maximum of +10.6%. Consistent with this, ΔScsO2, ΔDO2, ΔMVO2, ΔO2ER and ΔΩ responses indicated increasing mismatch of oxygenation balance outside the autoregulated zone. Changes in global OS-CMR were significantly correlated with all of these parameters (p≤0.02) except with ΔMVO2. CONCLUSION: OS-CMR offers a novel and non-invasive route to evaluate the effects of blood pressure variations, as well as of cardiovascular drugs and interventions, on global and regional myocardial oxygenation, as demonstrated in a porcine model. OS-CMR identified mismatch of O2 supply and demand below the lower limit of coronary autoregulation. Vasopressor induced acute hypertension did not compromise myocardial oxygenation in healthy hearts despite increased cardiac workload and O2 demand. The clinical usefulness of OS-CMR remains to be established.

Interdisciplinary Dialogue Is Needed When Defining Perioperative Recommendations: Conflicting Guidelines for Anesthetizing Patients for Pilonidal Surgery.

National or international guidelines can help surgeons and anesthesiologists make treatment decisions, but the existence of conflicting recommendations can hinder treatment rather than helping. A case in point is the treatment of pilonidal sinus disease, a chronic subcutaneous infection located in the sacrococcygeal area. Its incidence is rising, reaching almost 100/100,000 inhabitants. Three surgical societies have proposed guidelines for treating the disease, but these guidelines vary greatly in their approach to anesthesia. Who should provide input into guidelines? And how can medical disciplines successfully collaborate? Anesthesiologists must be involved in defining perioperative recommendations not only in patients with pilonidal sinus disease.