Time requirements for perioperative glucose management using fully closed-loop versus standard insulin therapy: A proof-of-concept time-motion study.

AIMS: To compare the time required for perioperative glucose management using fully automated closed-loop versus standard insulin therapy. METHODS: We performed a time-motion study to quantify the time requirements for perioperative glucose management with fully closed-loop (FCL) and standard insulin therapy applied to theoretical scenarios. Following an analysis of workflows in different periods of perioperative care in elective surgery patients receiving FCL or standard insulin therapy upon hospital admission (pre- and intra-operatively, at the intermediate care unit and general wards), the time of process-specific tasks was measured by shadowing hospital staff. Each task was measured 20 times and its average duration in combination with its frequency according to guidelines was used to calculate the cumulative staff time required for blood glucose management. Cumulative time was calculated for theoretical scenarios consisting of elective minor and major abdominal surgeries (pancreatic surgery and sleeve gastrectomy, respectively) to account for the different care settings and lengths of stay. RESULTS: The FCL insulin therapy reduced the time required for perioperative glucose management compared to standard insulin therapy, across all assessed care periods and for both perioperative pathways (range 2.1-4.5). For a major abdominal surgery, total time required was 248.5 min using FCL versus 753.9 min using standard insulin therapy. For a minor abdominal surgery, total time required was 68.6 min and 133.2 min for FCL and standard insulin therapy, respectively. CONCLUSIONS: The use of fully automated closed-loop insulin delivery for inpatient glucose management has the potential to alleviate the workload of diabetes management in an environment with adequately trained staff.

The First Reported Case of Lorlatinib-Associated Diabetic Ketoacidosis

Introduction: Lorlatinib is a third-generation tyrosine kinase inhibitor that inhibits anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1). Although 2-10% of patients with non-small cell lung cancer developed hyperglycemia in phase 2 and 3 studies of lorlatinib, only one case has subsequently reported hyperglycemia >500 mg/dL, and no cases of diabetic ketoacidosis (DKA) have been previously reported. Phase 1 trials in neuroblastoma are ongoing. Case Description: A 34-year-old woman with ALK-mutated paraspinal neuroblastoma presented with DKA 14 months after initiation of lorlatinib. Prior to starting lorlatinib, her hemoglobin A1c had been 5.0% (n: < 5.7%). After 12 months of therapy, her A1c increased to 7.8%, prompting the initiation of metformin 500 mg daily. However, two months later she was admitted for DKA with a blood glucose of 591 mg/dL (n: 65-99 mg/dL), CO2 17 mmol/L (n: 20-30 mmol/L), anion gap 18 (n: 8-12), moderate serum ketones, and 3+ ketonuria. Her A1c was 14.8%, C-peptide was 1.2 ng/mL (n: 1.1-4.3 ng/mL), and her glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies were negative. She was also found to be incidentally positive for COVID-19 but was asymptomatic without any oxygen requirement. The patient's DKA was successfully treated with IV insulin infusion, and she was discharged after 3 days with insulin glargine 27 units twice daily and insulin aspart 16 units with meals. One month later, her hemoglobin A1c had improved to 9.4%, and the patient's oncologist discontinued lorlatinib due to sustained remission of her neuroblastoma and her complication of DKA. After stopping lorlatinib, her blood glucose rapidly improved, and she self-discontinued all her insulin in the following 3 weeks. One month later, she was seen in endocrine clinic only taking metformin 500 mg twice daily with fasting and post-prandial blood glucose ranging 86-107 mg/dL. Discussion(s): This is the first reported case of DKA associated with lorlatinib. This case highlights the importance of close glucose monitoring and the risk of severe hyperglycemia and DKA while on lorlatinib therapy. Discontinuation of lorlatinib results in rapid improvement of glycemic control, and glucose-lowering treatments should be promptly deescalated to avoid hypoglycemia.Copyright © 2023

The Complexities of Managing Hypertriglyceridemia-Induced Pancreatitis in a Critically-Ill COVID-19 Patient

Introduction: Hypertriglyceridemia-induced pancreatitis (HTP) is a variant of pancreatitis requiring unique management. The complications of COVID-19 and its treatments can make HTP therapy more nuanced. This case describes a patient who presented in diabetic ketoacidosis (DKA) with HTP, and COVID-19. The patient developed renal and respiratory failure, necessitating hemodialysis (HD) and extracorporeal membrane oxygenation (ECMO), complicating an otherwise straightforward medical management plan. Case Description: A morbidly obese (BMI 38.9 kg/m2) 43-year-old male presented to an outside hospital with abdominal pain, and vomiting, and was found to have HTP with triglycerides (TG) >2000 mg/dL (<149 mg/dL) and presumed new-onset type 2 Diabetes (HbA1c 10.9%) with DKA. Treatment with fluids, intravenous (IV) insulin infusion and plasmapheresis were initiated. He developed hypoxia after receiving over 17 liters of fluids and was intubated, subsequently developing renal failure and was transferred to our tertiary center for HD and ECMO. On admission, he tested positive for COVID-19, rhabdomyolysis [creatinine kinase 5600 U/L (30-200 U/L)], HTP [TG 783 mg/dL (<149 mg/dL), lipase 461 U/l (7-60 U/L)], glucose 269 mg/dL (not in DKA), transaminitis [AST 184 U/L (4-40 U/L), ALT 61 U/L (4-41 U/L)] and renal failure (GFR 10 ml/min/1.73m2). IV insulin infusion was initiated for hyperglycemia worsened by COVID-19 dexamethasone treatment. Plasmapheresis was performed twice with minimal effect at maintaining a low TG. Fenofibrate was not initiated due to renal failure;Lovaza could not be given via oral gastric tube;Atorvastatin was attempted once rhabdomyolysis resolved, with subsequent worsening of liver function tests. Heparin infusion was initiated for deep vein thrombosis treatment and HTP but was stopped after development of heparin induced thrombocytopenia. The patient developed worsening hypoglycemia requiring cessation of IV insulin, hypotension requiring maximum pressor support, and worsening sepsis leading to his death. Discussion(s): This case illustrates the challenges of managing a patient with HTP and COVID-19. It demonstrates how a normally straightforward treatment algorithm can become increasingly complex when factoring the patient's comorbid conditions. The case highlights the importance of knowing both treatment indications and contraindications for HTP. In this case, HTP may have been the initial diagnosis, straightforward for most endocrinologists, but its treatments and comorbid conditions ultimately made the landscape more challenging, limiting effective management and ultimately leading to this patient's demise.Copyright © 2023

Performance of a Computerized Insulin Infusion Protocol in 359 Critically Ill Patients with COVID-19

Objective: People with diabetes and uncontrolled hyperglycemia are at high risk of COVID-19 complications and as such, many patients admitted to the ICU with COVID-19 have diabetes or stress hyperglycemia. It is suggested that quick and adequate control of hyperglycemia without increasing the risk of hypoglycemia is imperative to improve outcomes in these patients. Control of wide fluctuations of glycemic variances in these patients may often require modifications of existing strategies of glycemic management. Use of a computerized insulin infusion protocol (CIIP) in these settings could be largely beneficial in getting early and sustained glycemic control. We report our experience with the Lalani Insulin Infusion Protocol (LIIP), a novel CIIP with dynamic and adaptive glycemic targets in accordance with the patient's glycemic state, in critically ill COVID-19 patients with hyperglycemia treated with IV insulin. Method(s): We conducted a retrospective analysis of 359 critically-ill COVID-19 patients in whom LIIP was used (8/18/2020 to 08/31/2022) at six HonorHealth Hospitals in the Phoenix metropolitan area. Primary endpoints of the analysis included Time to Euglycemia (min), % of time in euglycemia (70-180 mg/dl), % of time in hyperglycemia (>180 mg/dl), and % of time in hypoglycemia (<70 mg/dl). We also report the average length of stay (ALOS) in the hospital and ICU as well as the discharge dispositions of these patients. Result(s): Of the 359 critically ill COVID-19 patients who received IV insulin directed by LIIP, 167 patients had diabetes, 266 patients were treated with steroids, 226 patients had compromised renal function (eGFR< 60), 40 patients had sepsis, and 5 patients had cardiovascular comorbidities. The following glucometrics were observed: average Time to Euglycemia from baseline glucose values was 278 minutes, average % time in euglycemia was 83.01%, average % time in hyperglycemia was 16.77%, and average % time in hypoglycemia was 0.22%. Of the 359 patients, there were 166 deaths (46.2%), 91 patients were discharged to home (25.4%), and 102 patients were discharged to an interim facility (28.4%). The hospital ALOS was 15.02 days and ICU ALOS was 9.50 days. Discussion/Conclusion: For HonorHealth hospitals, LIIP was a safe and effective method of quickly achieving and maintaining euglycemia in critically ill patients with COVID-19, while maintaining low hypoglycemia incidence. Herein the patients reported had varying degrees of comorbidities and treatments, including steroids and vasopressors;however, no modifications in glycemic management strategy or nursing workflow were necessary during the use of LIIP due to its adaptive formula which individualizes IV insulin rates for each patient.Copyright © 2023

Clinical Experience of Using Telemedicine for the Management of Patients Using Continuous Subcutaneous Insulin Infusion in a Highly Complex Latin American Hospital.

INTRODUCTION: Continuous subcutaneous insulin infusion (CSII) has emerged as a potential solution for diabetes management during the pandemic, as it reduces the need for in-person visits and allows for remote monitoring of patients. Telemedicine has also become increasingly important in the management of diabetes during the pandemic, as it allows healthcare providers to provide remote consultations and support. Here, we discuss the implications of this approach for diabetes management beyond the pandemic, including the potential for increased access to care and improved patient outcomes. METHODS: We performed a longitudinal observational study between 1 March 2020 and 31 December 2020 to evaluate glycemic parameters in diabetic patients with CSII in a telehealth service. Glycemic parameters were time in range (TIR), time above range, time below range, mean daily glucose, glucose management indicator (GMI), and glycemic variability control. RESULTS: A total of 36 patients were included in the study, with 29 having type 1 diabetes and 6 having type 2 diabetes. The study found that the proportion of patients achieving target glucose variability and GMI remained unchanged during follow-up. However, in patients with type 2 diabetes, the time in target range increased from 70% to 80%, and the time in hyperglycemia decreased from 2% to 0%. CONCLUSIONS: The results of this study suggest that telemedicine is a strategy for maintaining glycemic control in patients using CSII. However, the lack of access to the internet and adequate telemonitoring devices make it difficult to use on a large scale in emerging countries like ours.

COVID 19 Induced Hyperglycaemic Complications

Background: COVID 19 has two-way interaction with Type II Diabetes Mellitus. First, patient with DM are more prone for developing severe COVID 19. Second, moderate to severe COVID 19 can present with new onset DM or may lead to hyperglycaemia and hyperglycaemic complications in Type II DM patients. In this report we present 4 cases of COVID 19 associated Hyperglycaemic Complication (3 with Diabetic Ketoacidosis and 1 with Hyperglycaemic hyperosmolar state). Method(s): Case Series of patients admitted to Thumbay Hospital, Ajman. Result(s): We report 4 cases of COVID 19 patients who presented to us with hyperglycaemic complications. There of them had features of Diabetic Ketoacidosis and one had Hyperglycaemic hyperosmolar state. All were treated with IV Insulin infusion and IV Fluids. COVID 19 infection was managed as per MOH protocol. All patients recovered well and were discharged in stable condition. Discussion(s): COVID 19 is associated with new onset DM or may lead to hyperglycaemic complications in patients with Type II DM. There are three pathophysiological processes which may be responsible for this finding. One, SARS-CoV-2 virus is known to enter the body through angiotensin-converting enzyme (ACE) II receptors in the pulmonary pneumocytes leading to infection and inflammation. Similar ACE-II receptors are also expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, the small intestine, and the kidneys. Direct infection of pancreatic beta-cells with SARS-CoV-2 virus with beta-cell cell injury is likely the underlying mechanism for development of new onset diabetes and hyperglycaemia in existing diabetic patients. Such direct beta cell infection can cause hyperglycaemic complications in asymptomatic or mild COVID 19 as well. Two, moderate to severe COVID 19 is associated with hyperinflammatory immune response leading to marked rise in inflammatory mediators such as C-reactive protein and ferritin. Such hyperinflammatory response can also lead to hyperglyacemia in patients with diabetes mellitus. Three, corticosteroids are mainstay treatment of patients with moderate to severe COVID 19 and would definitely contribute to worsening of hyperglycaemia in these patients. Our patients presented to us with hyperglycaemic complications before initiation of any treatment. It is likely that such a situation would be due to direct infection and destruction of beta cells with SARS-CoV-2 virus infection. Conclusion(s): Type II Diabetes Mellitus patients are high risk of developing hyperglycaemic complications due to COVID 19. This can lead to increased morbidity and mortality. Patients with Type II DM should seek medical attention even if they have mild to asymptomatic COVID 19 to monitor for hyperglycaemic complication which can develop irrespective of severity of stage of illness.

The Impact of Covid-19 Pandemic on the Glycemic Regulation of Patients with Type 1 Diabetes Mellitus and Continuous Insulin Infusion Systems

Background and Aims: The COVID-19 pandemic severely affected the glycemic regulation of adult patients with type 1 diabetes (T1D). The aim of this study was to evaluate the impact of this pandemic on glycemic control in T1D patients with continuous insulin infusion systems (CSII). Method(s): A cohort of adult T1D patients with CSII was retrospectively evaluated. Data regarding number visits to our diabetes clinics, total daily insulin dose (TDID), blood and estimated HbA1c, time in range (TIR) (70-180mg/dl), time below range (TBR) (<70 mg/dl) time above range (TAR)(>180 mg/dl) and coefficient of variation (CV) in the pre- (March 2018- March 2020) and the pandemic (April 2020- April 2022) were collected. Result(s): 66 patients were studied (32 females, mean age 44 +/- 12.1 years, mean body mass index [BMI] 25.1 +/- 4 kg/m2, mean bHbA1c 7.3 +/- 0.9%, mean eHbA1c 7.15 +/- 0.9% and average number of 8 visits in the prepandemic period). During the pandemic period, TDID and BMI remained stable. On the contrary, TIR increased significantly (65.8 +/- 8.6 vs 70.2 +/- 16.8%;p = 0.026) while TBR (5.8 +/- 4 vs 4.9 +/- 3.8%;p = 0.007) and TAR (28.4 +/- 5.4 vs 24.9 +/- 3.3%;p = 0.03) diminished substantially. Furthermore, mean bHbA1c (7.3 +/- 0.9 vs 7.15 +/- 0.7%;p = 0.01), eHbA1c (7.15 +/- 0.9 vs 6.94 +/- 0.65%;p = 0.005) and CV (34.1 +/- 5.5 vs 31.7 +/- 4.1%;p < 0.001) decreased considerably during the pandemic. Additionally, the average number of visits was reduced to 4 per person but was positively associated with greatest improvement of glycemic control. Conclusion(s): Glycemic regulation of adult patients with T1D and CSII improved significantly during the pandemic, despite reduced visits to the diabetes outpatient clinics.

Outcomes in Patients with Diabetes Mellitus Affected by COVID-19

Background: An important prognostic factor in any form of infection seems to be glucose control in patients with diabetes mellitus. Therefore, we examined the effects of optimal glycemic control in patients with diabetes mellitus and affected by COVID-19. Interplay between severities of COVID-19 in earliest data on the pandemic. Relative risks of death 1.7 to 2.2 based on studies from China and Italy. People with diabetes appear to be at greater risk of severe disease. 31% mortality in Wuhan vs 14% hospitalized non DM. Most endemic related to T2DM rather than T1DM. Obesity and insulin resistance may be particular risk factors. Similar finding with previous SARS coronavirus outbreaks. (Ref, Wu, Jama 2020 Graselli Jama 2020 Zhon). Further study from France Coranado study including 1317 people with diabetes mellitus and COVID-19 in 53 hospitals, 88% with T2DM, 3% new diagnosis, mean BMI 28 kg/m2, HBA1c 65 mmol/mol. Primary endpoint death or ventilation at day 7. 410 required Intensive care unit admissions, 267 ventilated, 140 deaths and 237 patient discharged by day 7. Comprehensive dataset from UK comparing primary care and national diabetes audited data reported 33% of in hospital death related to COVID-19 occurred in people with diabetes (31.3% T2DM, 1.5% for type 1 diabetes). 5.1% of total individual population had diabetes. Adjusted relative risk of death of death 2.9% for type 1 diabetes, 1.8% for type 2 diabetes. It was also noted there is clear association between renal function and outcome with increased mortality with e GFR<60 ml/min/1.73 m2. Further data from the United States the authors further compared the outcome for those with hyperglycemia with those with normoglycemia at admission. 41% had poor outcome in those with hyperglycemia without known diabetes vs under 15% in context of COVID-19 for those with previous diabetes. Marked hyperglycemia at admission had strong impact on prognosis and the development of diabetes mellitus in context of COVID-19 is particular serious events. (Bode et al, J Diab Sci Tech, 2020). These worked was also identified a significant increase in total death in diabetes during 2020. Objective(s): To evaluate the effect of optimal glycemic control on the outcome for patients with type 2 diabetes affected by COVID- 19 infection. Method(s): This is a retrospective analysis of 100 patients with type 2 diabetes, who were affected by moderate disease of COVID-19 infection and admitted to Fujairah hospital (UAE), compared with 100 non diabetic patient admitted to the same hospital, with the same severity of COVID-19 disease. Result(s): Out of 200 patients studied, 100 patients were non-diabetic and 100 patients were having diabetes mellitus. In the diabetic group, all patients were diagnosed to have diabetes already before admission, and these 100 (100%) were treated with insulin infusion or basal -bolus regime. At baseline, D-dimer levels were not significantly higher in the diabetic group (mean D-dimer = 1.327) than in the normoglycemic group (mean of D-dimer = 1.544) (P < 0.001). Even though all patients were on standard treatment for COVID-19 infection, IL-6 and D-dimer levels persisted higher in patients with diabetes mellitus during hospitalization. Patients with diabetes had a higher risk of severe disease and prolonged length of stay and death 7% deceased (n=7), than those without diabetes and with normoglycemia.5% (n=5) deceased with length of stay of 13.7 days for diabetic group and 12.6 days for non-diabetic group. It was shown in our study, that there are contributory factors like hypertension which was found in 42% of our diabetic patients, and obesity that affect 34% of the same group, ischemic heart disease in three patients, could potentially contributed to the poor outcome and death. We looked to the effect of ethnicity in our patients outcome, the Emirati nationals contributed 14.29% (26) of the cohort, while 13.19% (n=24) were other Arab nationalities and 72.53% (n=132) were South-Asian (chart 5), it clearly showed those people of South-Asian background with high ctopic lipid and increased insulin resistance had worse outcome. Conclusion(s): Insulin infusion and basal/bolus regime was an effective method for achieving glycemic targets and improving outcomes in patients with COVID-19 and it was showed effect in reducing the rate of admission to an ICU, the use of mechanical ventilation and prevent death. Immediate evidence from our study, that COVID-19 was associated with particular challenges in diabetes management. High rate of ketosis and acidosis in people with type 2 diabetes (not normally, ketosis prone), extreme level of hyperglycemia and associated hyperosmolar. Associated with significant acute kidney injury in some cases. Extreme insulin resistance with very high insulin requirement. Many cases of new onset diabetes mellitus mostly required insulin. Some unusual biochemical features, marked fall in serum albumin, variable CRP, Ferritin response, raised D-dimer and high rate of thromboembolic complications. It was shown in our study, that there are contributory factors like hypertension, obesity, ischemic heart disease and presence of acute kidney injury, were potentially contributed to the poor outcome and death.

A Retrospective Cohort Analysis of Two Computerized Insulin Infusion Protocols.

OBJECTIVE: The primary objective of this analysis was to compare the safety and efficacy of a novel computerized insulin infusion protocol (CIIP), the Lalani Insulin Infusion Protocol (LIIP), with an established CIIP, Glucommander. METHODS: We conducted a 10-month retrospective analysis of 778 patients in whom LIIP was used (August 18, 2020 to June 25, 2021) at six HonorHealth Hospitals in the Phoenix metropolitan area. These data were compared with Glucommander that was used at those same hospitals from January 1, 2018 to August 17, 2020, n = 4700. Primary end points of the project included average time to euglycemia and average time in hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL). Additional subgroup analysis was done to evaluate CIIP performance in patients in whom maintenance of euglycemia was more challenging. RESULTS: The LIIP had a faster time to euglycemia (191 vs 222 minutes, P < .001) and similar time in hypoglycemia (2.79 vs 2.76 minutes, P = .50) for all patients, when compared with Glucommander. Similar observations were made for the following subgroups: diabetic ketoacidosis/hyperosmolar hyperglycemic state (DKA/HHS) patients, COVID-19 patients, patients on steroids, patients with ≥60 glomerular filtration rate (GFR), patients with renal insufficiency, and patients with sepsis. CONCLUSIONS: The LIIP is a safe and effective CIIP in managing intravenous insulin infusion rates. Utilization of LIIP resulted in reduced time to euglycemia, P < .001, when compared with Glucommander and did not cause increased hypoglycemia during the project period. Contributing factors to the success of LIIP may include improved clinical workflow, learnability and ease of use, compatibility with the Epic electronic health record (EHR), and its unique, dynamic and adaptive algorithm.

Application of the PDCA Cycle for Managing Hyperglycemia in Critically Ill Patients.

INTRODUCTION: Stress hyperglycemia is a common symptom in critically ill patients, and is not only a marker indicating the severity of illness but is also related to worsening outcomes. Managing stress hyperglycemia without increasing the likelihood of hypoglycemia is one of the most pressing challenges to be urgently addressed in clinics. The Plan-Do-Check-Act (PDCA) cycle management has been put forward in various surgical management scenarios, and has proven to be effective in the diagnosis and treatment of different diseases. It possesses dynamic characteristics and can be updated according to the results of glycemic control and feedback. This study focused on the use of PDCA to manage glucose levels in critically ill patients. METHODS: Based on the glucose level of 1003 critically ill patients admitted to the emergency intensive care unit (EICU) from 1 October 2019 to 31 December 2020, we collected and matched the prevalence of hyperglycemia, hypoglycemia, and glucose variability on a quarterly basis. According to the PDCA management method, we analyzed the possible causes, supervised the implementation of measures, summarized the feedback on improvements, and then proposed new improvement measures for implementation in the next quarter. RESULTS: Three measures were proposed and applied to enhance the management of hyperglycemia: (I) Updating and formulating three editions of the insulin infusion protocol and increasing the initial and maintenance doses of insulin on a case-by-case basis; (II) reducing the use of parenteral nutrition and ensuring that enteral nutrition is consumed at a uniform and slow rate; and (III) forming a training method during the COVID-19 pandemic and improving implementation of the insulin infusion protocol. Following PDCA management, the prevalence of hyperglycemia fell from 43.18% to 32.61%, the incidence of hypoglycemia was below 1.00%, and there was no significant fluctuation in blood glucose variability. CONCLUSION: The PDCA method is helpful in developing a superior insulin infusion protocol for critically ill patients and lowering the prevalence of hyperglycemia in critically ill patients.

A review of peri-operative diabetes care at Watford General Hospital

Diabetes affects around 15% of surgical patients and is associated with significant morbidity [1]. Poor peri-operative glycaemic control can result in longer hospital stays, up to 50% increased mortality and adverse postoperative outcomes including wound infection [1, 2]. Therefore, it is important to ensure diabetic peri-operative care is optimal, and as noted, in recent years, there is room for improvement. Methods A retrospective re-audit of electronic patient records was conducted to determine if peri-operative diabetic management was in line with local and national guidelines. We included all diabetic adults undergoing emergency or elective surgery, excluding obstetrics, in January 2022 at Watford General Hospital. Results Forty-seven of 618 (7.6%) patients who underwent surgery in January 2022 were diabetic adults meeting inclusion criteria. Of these 87% had type 2 diabetes, 51% were male and 55% were elective cases. Median age was 67 years (interquartile range 58-78.5 years). The majority (49%) were designated ASA status 2. Five of 21 elective cases had a glycated haemoglobin (HbA1c) result of > 69 mmol.l-1. Median surgical start time for elective diabetic patients was midday with 38% of cases occurring after midday. Starvation time was more than one missed meal or 12 h in 49% of patients. Variable rate intravenous insulin infusions (VRIIIs) were indicated in 43% of patients but only 10% received VRIIIs. Peri-operative blood glucose was maintained between 6-10 mmol.l-1 in 34% patients, 70% had intra-operative glucose monitoring but none hourly. Ketone testing occurred in one of two patients where indicated. Dexamethasone was given to 51% of patients (five of those were diet-controlled). Discussion A larger sample size was obtained on re-audit with 47 patients vs. 10 patients in January 2021, likely due to effects of the COVID-19 pandemic on elective surgery. Blood glucose monitoring pre- and postoperatively in diabetic patients has remained at least 70% in both audit cycles, but use of VRIIIs fell from 60% to 20%. We presented the findings at a clinical governance meeting and discussion of the guidelines identified that multiple documents and significant text acted as barriers to implementation. Therefore, we designed a flowchart to improve compliance and placed this in theatres and pre-operative areas. We hope this initiative, in addition to local teaching, will improve peri-operative diabetic care. We plan to re-audit and consider implementing further changes if care remains suboptimal. (Figure Presented).

Insulin Requirements for Patients With COVID-19 Presenting With Diabetic Ketoacidosis.

Introduction Recent literature has shown that patients with COVID-19 and diabetic ketoacidosis may require more aggressive treatment than those with diabetic ketoacidosis alone. The primary objective of this study was to assess if intravenous regular human insulin infusion requirements in patients with diabetic ketoacidosis differed between patients with or without COVID-19. Methods This retrospective cohort study evaluated patients with diabetic ketoacidosis who received intravenous regular human insulin infusion during the COVID-19 pandemic. The primary outcome was the amount of intravenous regular human insulin infusion requirements needed during the diabetic ketoacidosis episode. Results Of the 77 patients that met inclusion criteria, 35 were positive for COVID-19 and 42 were negative. The primary outcome of total intravenous regular human insulin infusion requirements needed during the diabetic ketoacidosis episode was not statistically significant and resulted in 1.79±0.61 units/kg/day in the COVID-19 positive group and 1.81±0.6 units/kg/day in the negative group (p=1). Secondary outcomes that were statistically significant between groups were the amount of fluids received in the first 24 hours, potassium supplementation, phosphate supplementation, acute kidney injury, and hypokalemia. Conclusion There was no difference in intravenous regular human insulin infusion requirements in the setting of diabetic ketoacidosis (DKA) between COVID-19 positive and negative patients.

Identification of Modifiable Causes of Hypoglycemia in the Icu

INTRODUCTION: Hypoglycemia is associated with increased mortality in the ICU. Studies have shown that modifiable causes of hypoglycemia may include antihyperglycemic medication, reduced caloric intake & change in nutrition without insulin adjustment. The primary objective of the study was to identify modifiable risk factors for hypoglycemia in our ICUs in order to decrease its incidence. METHOD(S): This was a retrospective review from July to September 2020 of adult ICU patients at a tertiary medical center with a hypoglycemic event (glucose < 80mg/dL) given intravenous rescue dextrose. Medical, surgical, cardiac & neuro ICU patients were included. Exclusion criteria were COVID-19, comfort measures & hyperkalemia. Descriptive statistics were used for statistical analysis. RESULT(S): A total of 56 out of 784 patients (median age 64;60.7% male) had 180 discrete hypoglycemic events. Common risk factors were nothing by mouth orders (NPO) at the time of the event (69.2%), a timeframe of 1900 to 0700 (64.2%), active insulin orders (48.3%), being within 24 hours of a procedure (42.8%) or 24 hours of admission (33.9%), or having AKI (42.8%), diabetes (39.3%) or sepsis (41.1%). Of the 48.3% of patients on insulin, 40% were on an insulin infusion, 39% sliding scale & 21% long-acting. As compared to weekdays, hypoglycemia occurred 37.5%, 87.5%, and 137.5% more often on weekend days, weeknights, and weekend nights, respectively. CONCLUSION(S): The most common iatrogenic risk factors for hypoglycemia in the ICU identified in this review were the initial 24 hours of ICU admission, active insulin orders and both periprocedural and NPO status. Hypoglycemia was more common overnight but this is also when daily BMPs are collected. Interventions such as dextrose-containing maintenance fluids while NPO, removal of periprocedural NPO at midnight orders, the addition of fingerstick checks to ICU admission order sets and when a patient is NPO, and cautious insulin use are warranted to help mitigate these events. This pharmacy resident project led to a multidisciplinary policy change to hold tube feeds for patients with an ET tube or trach immediately before they travel to a procedural area instead of at midnight, or 6 hours prior to procedures with planned airway interruption or NPO status needed for bowel cases.

BETA BLOCKER AND CALCIUM CHANNEL BLOCKER OVERDOSE COMPLICATED BY COVID-19 PNEUMONIA AND RENAL FAILURE IN A PATIENT WITH SEVERE OBESITY

SESSION TITLE: A Look Into Poisoning and Drug Overdoses SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: We present a case of a 64-year-old woman with severe obesity (BMI 53) who presented with shock after beta-blocker (BB) and calcium channel-blocker (CCB) overdose. CASE PRESENTATION: The patient presented after an intentional suicide attempt, taking multiple antihypertensive medications, including tablets of nifedipine 90mg, carvedilol 25mg, and losartan 100mg. She had also been experiencing shortness of breath and lower extremity pain for several days. Upon arrival, she was lethargic and minimally responsive, and was found to be in shock with a heart rate 63. She was intubated for airway protection and started on multiple vasopressors including norepinephrine, phenylephrine, vasopressin, dopamine and epinephrine for circulatory support. She was also found to be positive for SARS-CoV-2. She was given activated charcoal, received gastric lavage, and whole bowel irrigation. She received a bolus of regular insulin at 1U/kg, and subsequently started on a high-dose insulin infusion titrated to 11U/kg/h along with dextrose infusion and calcium gluconate. By day four of admission, vasopressor requirements had been reduced to only norepinephrine and the insulin infusion had been successfully discontinued. However, her hospital course was further complicated MRSA and Pseudomonas pneumonia, and renal failure requiring hemodialysis. She continued to develop refractory shock, and remained over 50 liters net positive. Her condition progressively deteriorated and her gross volume overload was difficult to manage, and ultimately expired on day ten of admission. DISCUSSION: The management of CCB and BB overdose has been studied, with hyperinsulinemic euglycemic therapy (HIET)1,2 as our choice. Our patient's decline was likely secondary to the high volumes of dextrose infusion required after HIET. With underlying renal failure, insulin clearance proved to be a significant challenge. Such severe obesity with a weight-based regimen resulted in over 1500U insulin/hr at any given point with our patient. Renal clearance is governed by a proportion of t/V, where t denotes length of a dialysis session and V the volume of fluid in the patient's body.3 Patients with significant volume would require extensive dialysis sessions and fluid balances would be challenging. Continuous renal replacement therapy (CRRT) was attempted later in her hospital course. However, the patient was not able to tolerate it as she had progressed to multiorgan failure. CONCLUSIONS: HIET has shown to be a successful management strategy for CCB and BB overdose. However, weight-based dosing can prove to be a challenge in patients with severe obesity. CRRT should be considered early in severely obese patients that undergo HIET, given the rapid accumulation of fluid secondary to the large-volume insulin and dextrose infusions. Further investigations should look into identifying maximal safe dosages of HIET, especially in severely obese patients. Reference #1: Cole JB, Arens AM, Laes JR, Klein LR, Bangh SA, Olives TD. High dose insulin for beta-blocker and calcium channel-blocker poisoning. Am J Emerg Med. 2018 Oct;36(10):1817-1824. doi: 10.1016/j.ajem.2018.02.004 Reference #2: Krenz JR, Kaakeh Y. An Overview of Hyperinsulinemic-Euglycemic Therapy in Calcium Channel Blocker and β-blocker Overdose. Pharmacotherapy. 2018 Nov;38(11):1130-1142. doi: 10.1002/phar.2177 Reference #3: Turgut F, Abdel-Rahman E, M: Challenges Associated with Managing End-Stage Renal Disease in Extremely Morbid Obese Patients: Case Series and Literature Review. Nephron 2017;137:172-177. doi: 10.1159/000479118 DISCLOSURES: No relevant relationships by Alejandro Garcia No relevant relationships by Vishad Sheth no disclosure on file for Andre Sotelo;

Rationalising glycaemic control in critically ill patients during the Sars-CoV-2 pandemic

Introduction: Poor glycaemic control is associated with worse outcomes in critically ill patients.1,2 A blood glucose target of 6-10 mmol/L was suggested by the NICE-SUGAR trial. In the context of hyperglycaemia, this target is achieved utilising variable rate insulin infusions (VRIIs). Furthermore, there is increasing evidence that critically ill patients with SARS -CoV -2 infection suffer more complications if they are diabetic or have altered glycaemic control.3 Through a series of Plan-Do-Study-Act (PDSA) cycles, we attempted to improve the glycaemic management of critically ill patients in our Intensive Care Unit (ICU) over the last twelve months. Objectives: Through a retrospective multi-cycle audit and QI project we sought to: 1. Identify our diabetic patient demographics 2. Understand our current practices around use of VRIIs and rationalising of glycaemic management upon discharge from ICU 3. Improve documentation of glycaemic management plan upon discharge. 4. Actively collaborate with the Endocrinology team to produce local guidance. Methods: The RAH is a 7 bedded Level 3 ICU which admitted 324 patients between August 2020 and August 2021. All ICU survivors with a length of stay >24 hours were included. Data was collected retrospectively at the end of each cycle via ICCA Carevue between September 2020 and August 2021 in three cycles. Cycle 1 September 2020-December 2020, Cycle 2 January 2021-May 2021 and Cycle 3 June 2021-Ongoing. Intervention 1 (post cycle 1): Presentation of baseline data to department Intervention 2 (post cycle 2): Addition of Glycaemic Management plan to ICU discharge form on ICCA Carevue Intervention 3 (mid cycle 3) Creation of Guidance on Glycaemic Management at discharge from RAH ICU departmental guide created Results: Cycle 1 results: 56 eligible patients 14 of which were diabetic. 12 of these diabetic patients were discharged on a VRII. Three patients (25%) had a documented glycaemic management plan upon discharge. Cycle 2 results: 60 eligible patients, 17 were diabetic. 11 of these diabetic patients were discharged on VRII. Six patients (54.5%) had a documented glycaemic management plan upon discharge. Cycle 3 results: eligible patients, 11 were diabetic. 9 of these diabetic patients were discharged on a VRII. Eight patients (88.8%) had a documented glycaemic management plan upon discharge. Conclusion: Using PDSA cycles and Quality Improvement methodology, we have demonstrably improved the percentage of diabetic ICU patients with documented glycaemic management plans upon discharge. We have also encouraged formulation of a clear glycaemic plan and involvement of the endocrinology team upon discharge ensuring opportunities are not missed to reduce downstream VRII use where possible. The above guidance document has been a collaborative process between ICM and Endocrinology ensuring that support is available for doctors in ICU. Randomised control studies such as SWEET-AS have highlighted the long-term impact of diabetes in ICU survivors. 4 Our QI work confirms that it is important to understand the needs of the local population and ensure robust guidance is in place when optimising patient's glycaemic control safely.

DIABETIC KETOACIDOSIS IN A NEW ONSET ELDERLY TYPE 1 DIABETES AFTER SARS-CoV-2 VACCINATION: ASSOCIATION OR COINCIDENCE?

Introduction In the era of the COVID-19 pandemic, several cases of new onset diabetes associated with COVID-19 have been reoprted. Additionally, patients with diabetes, a high-risk population, are prioritised for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. The vaccine against the (SARS-CoV-2) could represent a new environmental trigger for autoimmune disorders such as Graves' disease, immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain-Barré syndrome, systemic lupus erythematosus and type 1 diabetes. case We report a case of diabetic ketoacidosis in a new onset Type 1 diabetes in an elderly female following SARSCoV- 2 vaccination. A 69-year-old female with a history of treated TB abdomen in 2015 with no history of diabetes received her second dose of SARS-CoV-2 vaccination (COMIRNATY) on 21st August 2021. Two weeks following vaccination, she developed osmotic symptoms, reduce appetite and lethargy. Her random blood glucose (RBS) was 41 mmol/L, serum ketone 4.4 mmol/L, pH of 7.29 mmHg, bicarbonate 12.5 mmol/L and serum osmolarity of 298 mOsm/kg. She was treated for DKA with intravenous insulin infusion and hydration with resolution of DKA within 12 hours. Anti-Glutamic Acid Decarboxylase and anti-Islet Cells antibodies were positive with low fasting C-peptide of 102 pmol/L. She was discharged well with basal bolus insulin. Four months later, HbA1c reduced from 15.6% to 7.7% with a random C-peptide of 152 pmol/L. Conclusion The occurrence of hyperglycaemia crisis following SARSCoV- 2 vaccine in patients with pre-existing diabetes is known but the occurrence of new onset autoimmune diabetes following vaccination is rare. Further studies are needed to better understand the underlying pathogenesis of autoimmune diabetes following SARS-CoV-2 vaccine.

CHALLENGES IN FLUID MANAGEMENT OF AN END-STAGE RENAL DISEASE PATIENT WITH COVID-19 PNEUMONIA AND STARVATION KETOACIDOSIS

INTRODUCTION Fluid management is a delicate process when it involves an anuric end-stage renal disease (ESRD) patient on regular hemodialysis, who has Coronavirus Disease-19 (COVID-19) pneumonia in acute respiratory distress syndrome (ARDS). The management is made even more challenging when the condition of the patient is complicated with starvation ketoacidosis. There is limited literature with regards to this issue. CASE We report the case of a 55-year-old male patient with ESRD, who is suffering from COVID-19 pneumonia in ARDS with concomitant starvation ketoacidosis. CONCLUSION Starvation ketoacidosis is an under-recognized cause of metabolic acidosis and may occur even in a diabetic patient who has been acutely unwell with poor oral intake. While the mainstay of therapy in a patient with starvation ketoacidosis is to provide an intravenous dextrosecontaining fluid replacement, this has to be judiciously given in an anuric ESRD patient on fluid restriction. A careful balance between low-dose insulin infusion to maintain euglycemia and strict fluid management is crucial to stop gluconeogenesis and ketogenesis. The ultimate goal is to bring the patient out of starvation ketoacidosis while avoiding the deleterious effect of fluid overload in a patient who is already in ARDS.

Assessing an Insulin Infusion Protocol and Calculator on Hyperglycemic Outcomes in the ICU During the COVID-19 Pandemic

Introduction: Hyperglycemia is associated with worse outcomes in the intensive care unit (ICU). Data suggests COVID-19 patients have poorly controlled glucose levels and an increased need for a calculator-based insulin infusion protocol. Studies examining the use of insulin calculators achieved consistent target blood glucose values with minimal episodes of hypoglycemia. Research Question or Hypothesis: Did implementation of an insulin infusion calculator and protocol reduce time to target blood glucose range and reduce the number of hypoglycemic events in the ICU during the COVID-19 pandemic? Study Design: An IRB-exempt retrospective cohort study examining patients treated with an insulin infusion before and after the implementation of an insulin infusion protocol and calculator. Methods: Reports of insulin infusion orders were pulled from the computerized patient record system. Data were collected from January 1, 2021 to August 31, 2021 (pre-intervention group) and November 1, 2021 to March 18, 2022 (post-intervention group). If patients were not located in the ICU or initiated on an insulin infusion, they were excluded from the study. The primary outcomes were time to target blood glucose range and number of hypoglycemic events. Results: There were 51 patient encounters analyzed, with 24 patients in the pre-intervention group and 16.7% with a current COVID-19 infection at time of admission. There were 27 patients in the postintervention group and 18.5% with a current COVID-19 infection. The average time to target blood glucose was 12.9 hours in the pregroup and 4.1 hours in the post-group. In the post-group, 12 patients experienced 46 hypoglycemic events with 10 events (21.7%) being severe hypoglycemia (< 40mg/dL). In the post-group, 9 patients experienced 24 hypoglycemic events, with 3 events (12.5%) being severe. Conclusion: Implementation of an insulin infusion protocol and calculator led to a lower incidence of hypoglycemic events and reduced time to target blood glucose range in the ICU.

Perioperative management of glycaemic control: still room for improvement

Introduction: Following a change in national diabetic guidance [1,2], local audit performed in 2019 identified areas of improvement which were incorporated into a revised care pathway for elective caesarean section (ELCS) in 2020. Shortly after introduction, the COVID-19 pandemic led to telephone (rather than face-to-face) pre-assessment. We performed a re-audit in 2021 to assess the impact of the new pathway and pre-assessment changes. Methods: Following local audit registration, retrospective notes review of all diabetic mothers having ELCS (22/11/21–24/12/21) was performed and results compared to the previous audit (2019) and national recommendations [1,2]. Results: Notes were available for all 10 women having ELCS in 2021 and compared to 10 women in 2019. In 2021 all women had gestational diabetes (GDM) and treatment included diet control (3), metformin alone (5), or insulin and metformin (2). In 2019, eight women had GDM and two were type-1 diabetics, with treatment including diet control (3), metformin alone (2), insulin alone (1) and dual insulin and metformin (4). The revised care pathway advised variable rate insulin infusion for all diabetics with blood glucose >7 mmol/L. In 2021, no women required a VRII, compared to two in 2019 due to type one diabetes and blood glucose over 9 mmol/L. In both audits, all women were admitted on the day of surgery and had ELCS under spinal anaesthesia. A comparison of the audit results in 2019 and 2021 is shown (Table). (Table Presented) Discussion: Despite a revised care pathway, guideline compliance for perioperative management of diabetic women having ELCS did not improve, although no woman had a documented blood glucose >7 mmol/L. Compliance was poor in all areas of perioperative management. We now plan to relaunch the pathway in all perioperative clinical areas to improve awareness. This re-audit highlights the importance of reviewing clinical practice to assess the impact of the pandemic on service improvements in perioperative obstetric care.

An Unusual Case of Autoantibody-Negative KetosisProne Diabetes (KPD) Secondary to Marked Insulin Resistance

KPD is classically regarded as an atypical form of diabetes caused by near-complete beta-cell failure. A 37-year-old Egyptian man (BMI: 27.7 Kg/m2) presented with hyperglycemia (362 mg/dL) and DKA (arterial pH 7.20, ketonemia 5.0 mmol/L, ketonuria 80 mg/dL) . He was afebrile, with recent polyuria, polydipsia and weight loss. HbA1c was 107 mmol/mol (11.9%) and blood tests excluded diabetes secondary to endocrinopathies. SARS-CoV-2 RT-PCR test was negative. IV insulin infusion (0.1 IU/kg/h) and IV fluid therapy were started. He was shortly transitioned to a sc basal-bolus insulin regimen (0.7 IU/kg/day) . Mixed-meal tolerance test (MMTT) revealed a peak 120-min stimulated C-peptide of 12.3 ng/mL, suggesting marked insulin resistance. Islet autoantibodies (ICA, IAA, GADA, IA-2A, ZnT8A) and insulin receptor autoantibodies (IgG/IgM) were negative. HLA genotyping detected the following haplotypes: DRB1∗01, ∗04;DQA1∗01:01P, ∗03:01P;DQB1∗03:02P, ∗05:01P. Insulin dose was gradually reduced and insulin therapy was discontinued after 4 months in favor of metformin (2550 mg/day) plus sc semaglutide (up to 1 mg/week) . After one year, MMTT revealed a peak 60-min stimulated C-peptide of 8.25 ng/mL. During the 18-month follow-up period, fasting capillary beta-hydroxybutyrate values were <0.2 mmol/L and HbA1c remained <48 mmol/mol (<6.5%) , indicating disease remission. This case suggests the existence of an autoantibody-negative KPD subtype driven by marked insulin resistance rather than by insulinopenia.