High-dose Insulin Therapy Research Articles

7305 Pheochromocytoma Presenting With Resistant Hyperglycemia

Abstract Disclosure: M. Economou: None. A. Devine: None. Background: Pheochromocytoma is a rare catecholamine producing tumor arising from the adrenal gland. Impaired glucose tolerance is a well-recognized hormonal and metabolic manifestation of pheochromocytoma caused by catecholamine excess [1]. Insulin resistance requiring very high doses of insulin in association with pheochromocytoma is, however, rare. Here we report a case of pheochromocytoma in a woman with diabetes mellitus that proved difficult to control despite high-dose insulin therapy. Case presentation: A 72-year-old woman with a longstanding history of type 2 diabetes mellitus, uncontrolled hypertension, hyperlipidemia and CVA presented to the hospital after she was found to have a hemoglobin of 7.0 ng/mL on routine labs. Notably, over the past 4 years, her insulin requirement gradually increased from 20 units/day to 50 units/day despite an A1c level of 6.1%. On presentation, our patient was hypertensive to 170/90 with limited response to multiple antihypertensive medications. Additionally, her glucose was severely uncontrolled, fluctuating between 200-500 mg/dL. Within days, the patient’s total daily insulin requirement increased tremendously to as much as 300 units/day. As part of her anemia workup, she underwent a contrast-enhanced CT abdomen & pelvis which identified a left adrenal mass measuring 2.2 x 2.8 x 2.9 cm. Further evaluation with MRI confirmed an adrenal mass suspicious for pheochromocytoma. Evaluation of plasma hormone levels revealed an elevated normetanephrine level of 7.10 nmol/L (normal: less than 0.89 nmol/L). Furthermore, the 24-h urinary normetanephrine level and chromogranin A levels were elevated to 145 mcg/day and 1203 ng/mL, respectively. Initial treatment with alpha and beta blockade improved blood pressure but glucose levels remained persistently elevated. The patient underwent left laparoscopic adrenalectomy and pathology revealed pheochromocytoma, measuring, 3.2 cm in diameter, with stains positive for CD56, synaptophysin and chromogranin. Surgical resection margins were negative for tumor. Postoperatively, insulin requirements returned to roughly that of her baseline, 40 units/day. Conclusion: Impaired glucose tolerance is a known phenomenon associated with pheochromocytoma. Despite this, it is unusual to see an insulin requirement rise as abruptly and drastically as seen in this case. Our patient, with relatively controlled diabetes had an enormous increase in her insulin requirement during her hospital course as evidenced by her insulin regimen which increased sixfold. This case highlights the importance of maintaining a high degree of suspicion for pheochromocytoma in patients with a sudden rise in insulin requirement and uncontrolled hypertension. Reference: (1) Ronen JA, Gavin M, Ruppert MD, Peiris AN. Glycemic Disturbances in Pheochromocytoma and Paraganglioma. Cureus. 2019 Apr 27;11(4): e4551. Presentation: 6/3/2024

From high dose Insulin therapy to dual oral therapy: recovery from glucotoxicity after acute pancreatitis and severe ketoacidotic hyperglycaemia

From high dose Insulin therapy to dual oral therapy: recovery from glucotoxicity after acute pancreatitis and severe ketoacidotic hyperglycaemia

De-Intensification from Basal-Bolus Insulin Therapy to Liraglutide in Type 2 Diabetes: Predictive Value of Mean Glycaemia during Fasting Test.

Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (-6.4 ± 19.7 vs. -3.4 ± 22.9 mmol/mol) and weight loss (-4.6 ± 7.1 vs. -2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation.

A Narrative Review Unveiling Novel Molecular Targets in Advancing Antidiabetic Medications: An Emerging Perspective

Diabetes Mellitus (DM) is a persistent metabolic disorder characterised by elevated glucose concentration in blood. Approximately, 422 million individuals globally suffer from diabetes, with the majority residing among middle-class and lower-class countries as per the reports of World Health Organisation (WHO) 2023. Strict blood sugar control in conjunction with high-dose insulin therapy might potentially prevent or delay the progression of microvascular issues, lower overall mortality, and lessen the chance of macrovascular problems. These conclusions were supported by the Diabetes Control and Complications Trial and the large longitudinal investigation known as the epidemiology of diabetes and its complications. Numerous drugs and receptors involved in glucose metabolism are currently being used to treat diabetes, including α-Glucosidase inhibitors, dopamine D-2 agonists, biguanides, glinides, amylin analogues, Peroxisome Proliferator-activated Receptors (PPARs), Glucagon-like Peptide-1 (GLP-1), and biguanides. Due to the associated side effects and the financial difficulties in obtaining traditional antidiabetic regimens, the current review has placed a higher priority on investigating novel molecular targets for the development of antidiabetic medications intended to manage the progression of the illness. This emphasises how important it is to find new molecular targets associated with the illness’s onset instead of only treating its symptoms or outward signs.

Accuracy of the Nova StatStrip® glucometer in patients undergoing major abdominal surgery: an observational study.

While the Nova StatStrip® Glucose Hospital Meter System (Nova Biomedical, Waltham, MA, USA) is approved for point-of-care testing (POCT) in critically ill patients, its use during major abdominal surgery has not been evaluated. The purpose of this study was to assess the accuracy of the Nova StatStrip glucometer in patients undergoing major hepatobiliary procedures using the Parkes error grid (ISO15197:2013) and criteria defined by the Clinical and Laboratory Standards Institute (CLSI) POCT12-A3 guideline. This study was a post hoc exploratory study of patients participating in a prospective randomized controlled trial on the effects of hyperinsulinemic normoglycemia (HNC) on infectious outcomes after hepatobiliary surgery. Arterial blood samples were collected before surgery and one hour, two hours, and three hours after baseline. Blood glucose levels were analyzed by the Nova StatStrip glucometer and the GEM® PremierTM 5000 blood gas analyzer. Accuracy of the StatStrip glucometer was assessed using the Parkes error grid for type 1 diabetes mellitus (when 99% of samples were within zones A and B on the Parkes error grid and clinical accuracy was acceptable) and the CLSI POCT12-A3 criteria. Blood glucose levels were analyzed in 135 patients, 70 of whom received the HNC. In the Parkes error grid plotted, all samples at all time-points were within zones A and B. The Nova StatStrip glucometer also satisfied CLSI POCT12-A3 criteria at all time-points. The Nova StatStrip glucometer was accurate in patients undergoing major upper abdominal surgery, independent of the administration of high-dose insulin therapy. ClinicalTrials.gov (NCT01528189); registered 7 February 2012.

Insulin concentrations following termination of high-dose insulin euglycemic therapy

Introduction High-dose insulin therapy is used in patients with calcium channel blocker and beta-adrenergic antagonist overdoses. The pharmacokinetics of insulin are scantly reported following high-dose insulin therapy. We present two cases of persistently elevated insulin concentrations following high-dose insulin therapy. Case reports A 50-year-old woman and a 45-year-old man experienced hypotension after overdosing on amlodipine and atenolol. They were treated with high-dose insulin therapy for 54 hours at 2 units/kilogram/hour and 48 hours at 10 units/kilogram/hour, respectively. Following termination, serum insulin elimination was studied. Insulin concentrations remained greater than 1,000 µU/mL (fasting reference 2.6–24.9 µU/mL) for longer than 4 hours (case 1) and 11 hours (case 2) and greater than 300 µU/mL for longer than 8 hours and 21 hours, respectively. Insulin concentrations decreased with apparent first-order elimination half-lives of 13.0 hours and 6.0 hours. Discussion Following high-dose insulin therapy, insulin concentrations remained elevated for longer than expected based on normal pharmacokinetics in therapeutic dosing. Three previous cases reported insulin half-lives of between 2.2 hours and 18.7 hours. The current cases add to the existing data that insulin has a variable but prolonged half-life following high-dose insulin therapy. Conclusions These findings suggest that patients are at prolonged risk of hypoglycemia following cessation of high-dose insulin infusions.

Treatment Modalities in Calcium Channel Blocker Overdose: A Systematic Review.

Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.

RF19 | PSUN368 Surviving Insulinoma: Severe Insulin Resistance in the Face of Endogenous Hyperinsulinemia

Abstract Introduction Insulinoma is a rare pancreatic neuroendocrine tumor (PNET) accounting for 1-2% of pancreatic neoplasms. Usually benign, even small tumors can cause significant morbidity due to hypoglycemia. Surgical resection is preferable choice of treatment, but diagnosis is usually delayed and localization can be evasive. We present a case of insulinoma in a patient who battled his symptoms with high carbohydrate intake leading to massive weight gain associated with severe insulin resistance. Case A 70 year old male presented to the ED after being found unconscious in his home. Blood glucose was 34 mg/dl after missing a meal. He had a remote history of diabetes mellitus, which gradually resolved. Five years ago, he began experiencing sweats, tremors, headaches and confusion early in the morning or when fasting that improved with eating. He was hospitalized four years ago due to hypoglycemia where he was suspected to have endogenous hyperinsulinemia. CT abdomen at that time was unremarkable. Possibility of insulinoma was raised, but patient did not pursue further investigations. In the last 4 years, he avoided severe hypoglycemic events with frequents meals, but had gained more than 50 lbs with resultant BMI of 51 kg/m2. While admitted, he underwent a 72h fasting test showed glucose 42 mg/dl, insulin level was 84.8 IU/L (range &amp;lt;3), proinsulin was 105.7 (pmol/l) and C-peptide was 4.83 ng/ml (ref &amp;lt;0.2). EUS revealed 7 mm×4 mm mass in pancreatic body. FNAB confirmed well differentiated PNET, grade 1. CT abdomen remained unrevealing. He was started on weight based diazoxide therapy with resolution of hypoglycemic events and persistent hyperglycemia, which required high dose insulin therapy and improved with significant decrease in diazoxide dose. Hospitalization was complicated by hypoxic hypercarbic respiratory failure due to obesity hypoventilation syndrome, COVID19 infection and new onset rapid atrial fibrillation. Patient was deemed not to be a surgical candidate due to multiple comorbidities and his medical management was switched to octreotide with low dose insulin therapy, which patient tolerated well. Conclusion Diagnosis of insulinoma can be significantly delayed in cases with mild or slowly progressive course of the disease. We suggest that progressive development of severe insulin resistance in patients with baseline obesity and insulin resistance-driven DM2 can mask endogenous hyperinsulinemia for extended period of time. This gives a false sense of slower progression or even resolution of symptomatology, as well as diversion to alternative diagnoses, like postprandial hypoglycemia. We also argue that "resolution" of diabetes with significant weight gain, especially when associated with increased calorie intake through frequent meals and symptomatology suggestive of hypoglycemia should be a red flag for workup towards possible insulinoma, akin to suspecting adrenal insufficiency in diabetic patients with an unexplained decrease in insulin requirements. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.

Acute glycogenic hepatopathy in pregnancy: a case report and literature review

Abstract Objectives Acute glycogenic hepatopathy (AGH) is a rare complication of poorly controlled diabetes mellitus. This is the first report in the English literature describing accurate diagnosis and management of AGH during pregnancy. Case presentation A 46 year-old gravida 4 para 2 presented at 30 weeks gestation with uncontrolled diabetes, ketoacidosis, and severe hypertension. Euglycemia and normotension were achieved within 24 h of admission but serum transaminase levels which had been normal on admission increased to a very high level over several days, and then resolved spontaneously. Conclusions AGH may occur during pregnancy and should be considered in the context of chronic poorly controlled overt diabetes, rapid normalization of maternal blood glucose levels following high dose insulin therapy, and unexplained new-onset serum transaminase levels elevation. Accurate diagnosis is important because the correct treatment is conservative management, not delivery.

Glucose control using an artificial pancreas in a severe COVID-19 patient on extracorporeal membrane oxygenation: a case report

The usefulness and safety of continuous glucose monitoring (CGM) systems in adult patients with severe coronavirus disease (COVID-19) have been reported. Using CGM might reduce the exposure patients and healthcare workers to COVID-19 and limit the use of personal protective equipment during the pandemic. CGM devices measure glucose in the subcutaneous interstitial fluid, but the accuracy of this technique has not been established in critically ill patients. The artificial pancreas, STG-55 (Nikkiso, Tokyo), is a closed-loop device that conducts continuous blood glucose monitoring using a peripheral vein. We used the STG-55 for glucose control in a 60-year-old woman with severe COVID-19 admitted to the intensive care unit. Due to severe respiratory failure, the patient was intubated, and extracorporeal membrane oxygenation was introduced. Because she had hyperglycemia despite high-dose intravenous insulin therapy, we decided to use STG-55 for glucose control. The STG-55 safely titrated the insulin infusion and monitored glucose levels. Fifty-six hours after adopting the STG-55, it was removed because the blood sampling failed. No episodes of hypoglycemia were observed despite deep sedation during this period. In conclusion, this case demonstrates the potential utility of an artificial pancreas in patients with severe COVID-19.

Evaluating the Impact of Glucagon-Like Peptide-1 Receptor Agonists on Metabolic Changes in Patients With Type 2 Diabetes on High-Dose Insulin.

Studies involving the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide have shown reductions in hemoglobin A1c (HbA1c), weight, and insulin requirements in patients with type 2 diabetes mellitus (DM2) requiring high-dose insulin therapy. The effect of the class of GLP-1 RAs on these parameters is unknown. A retrospective cohort analysis was conducted in patients with DM2 where a GLP-1 RA was added to high-dose insulin therapy. The primary composite outcome was the change from baseline to 9 months in HbA1c, weight, and insulin dose. GLP-1 RA therapy was associated with a significant reduction in HbA1c from baseline (-0.9%; P = 0.022). Weight and insulin dose were not significantly reduced from baseline. There was a moderate effect of individual agents on these outcomes, but no significant reductions were seen due to the small sample size. Generalizability of these findings may be limited by the characteristics and size of the study population. The effect of GLP-1 RA therapy on HbA1c may be attributed to the medication class. The effect of individual agents on weight and insulin requirements needs further investigation.

872: Prolonged Hypoglycemia Following High-Dose Insulin Therapy as a Treatment Modality for Overdose

872: Prolonged Hypoglycemia Following High-Dose Insulin Therapy as a Treatment Modality for Overdose

CPD article: Poisons affecting the cardiovascular system

Cardiac and cardiovascular function can be affected by numerous substances, including overdose of drugs for cardiac and cardiovascular conditions, drugs used in the management of other diseases, over-the-counter medicines and supplements, foods and natural toxins such as plants. A common cause of tachycardia in dogs is exposure to salbutamol from piercing an asthma inhaler. Cardiac drugs such as beta-blockers and calcium-channel blockers can cause hypotension and disrupt cardiac rhythm. Although severe cases are not common in companion animals, management may be complex, requiring high dose insulin therapy and/or lipid emulsion therapy. The methylxanthines caffeine and theobromine, which are found in foods, and caffeine in supplements, are readily accessible to pets and can cause central nervous system and muscle (including cardiac muscle) stimulation. Animals with pre-existing cardiac disease or those with a mixed cardiotoxic drug overdose are likely to be more at risk of effects after exposure to substances affecting the cardiovascular system. Support of cardiac and cardiovascular function is essential to prevent cardiac injury and maintain tissue perfusion. Specific management depends on the severity of clinical signs and the particular substance involved.

Poisons affecting the cardiovascular system

Cardiac and cardiovascular function can be affected by numerous substances, including overdose of drugs for cardiac and cardiovascular conditions, drugs used in the management of other diseases, over-the-counter medicines and supplements, foods and natural toxins such as plants. A common cause of tachycardia in dogs is exposure to salbutamol from piercing an asthma inhaler. Cardiac drugs such as beta-blockers and calcium-channel blockers can cause hypotension and disrupt cardiac rhythm. Although severe cases are not common in companion animals, management may be complex, requiring high dose insulin therapy and/or lipid emulsion therapy. The methylxanthines caffeine and theobromine, which are found in foods, and caffeine in supplements, are readily accessible to pets and can cause central nervous system and muscle (including cardiac muscle) stimulation. Animals with pre-existing cardiac disease or those with a mixed cardiotoxic drug overdose are likely to be more at risk of effects after exposure to substances affecting the cardiovascular system. Support of cardiac and cardiovascular function is essential to prevent cardiac injury and maintain tissue perfusion. Specific management depends on the severity of clinical signs and the particular substance involved.

Management of Severe Beta-Blockers Toxicity with High Dose Insulin Euglycemic Therapy: A Case Report

Aims: Highlighting the efficacy of early initiation of high dose insulin therapy in Beta-blockers overdose over conventional therapy.&#x0D; Presentation of Case: Authors describe the successful treatment of severe bisoprolol-induced cardiogenic shock in a 74-year-old man using high dose insulin euglycemic therapy. He received intravenous bolus of 1IU/kg of actarapid insulin followed by intravenous infusion of 0.5 IU/kg/hour. The patient hemodynamic parameters improved dramatically within few hours after starting the insulin therapy.&#x0D; Discussion: Beta-blockers overdose can lead to significant morbidity and mortality due to the often-associated vasopressor-resistant shock. high dose insulin euglycemic therapy is a potential emerging therapy for beta-blockers toxicity with support in the literature from several animal studies, case reports and expert opinion.&#x0D; Conclusion: High dose insulin euglycemic therapy is a safe and effective method in reversing the hemodynamic consequences induced by beta-blockers overdose and should be used early in the treatment.

Treatment Patterns and Characteristics of Individuals Initiating High-Dose Insulin for Type 2 Diabetes Mellitus.

Few studies have examined patient characteristics and treatment patterns of high-dose insulin therapy (> 200 units/day) among patients with type 2 diabetes mellitus (T2DM). To understand patient characteristics, dosing, adherence, and persistence related to high-dose insulin therapy. This was a retrospective observational study that used administrative claims from a large national health plan. Patients were identified who had been diagnosed with T2DM and who were aged 18-89 years, enrolled in a commercial or Medicare Advantage Prescription Drug plan, newly initiated on a total daily dose (TDD) > 200 units of insulin between January 2011 and August 2015. Patients were required to be enrolled 6 months before and 12 months after the index date. Patients were categorized to Regimen-100 if treated with U-100 insulin only or Regimen-500 if treated with U-500R with or without U-100. Baseline demographic and clinical characteristics were evaluated. An adjustment factor for the days supply was calculated as the ratio of median time between insulin claims, and median pharmacy reported days supply for each insulin prescription. Adjusted days supply, quantity, and concentration were used to calculate TDD for each quarter after the index date. Adherence was measured as the proportion of days covered (PDC) for each regimen. Persistence was measured in 2 ways: the percentage of patients remaining on index medications in each quarter and the proportion of patients who maintained TDD > 200 units during all 4 quarters of the 12-month post-index period. We identified 2,339 patients newly titrated up to TDD > 200 units on either Regimen-100 (2,062, 88.2%) or Regimen-500 (277, 11.8%). Patients on Regimen-500 were slightly younger with higher prevalence of comorbidities. The mean TDD (SD) for Regimen-100 decreased from 228.6 (36.0) units during the first quarter to 194.2 (181.4) units during the last quarter. The mean TDD (SD) for Regimen-500 increased from 294.2 (102.2) units in the first quarter to 304.8 (281.6) units in last quarter. The average adherence to the high-dose insulin regimen was 68.2% (30.7; median 72.6%) for the Regimen-100 cohort and 75.5% (27.0; median 85.2%) for the Regimen-500 cohort. In the Regimen-100 and Regimen-500 cohorts, 45.3% and 55.2% had a PDC ≥ 80%, respectively. Only 23.0% and 51.6% of patients maintained TDD > 200 units for the Regimen-100 and Regimen-500 cohorts, respectively, throughout the 4 quarters after the index date. We observed that many patients did not maintain high-dose insulin use over time, especially those on standard U-100 insulin only. This dosing pattern appears to reflect the differences in patient characteristics, insulin needs, and adherence/persistence behavior between those on Regimen-100 and those on Regimen-500. This study was supported by funding from Eli Lilly and Company to Humana as a collaborative research project involving employees of both companies. Chen, Brown, Fan, Taylor, and He are employees of Eli Lilly and Company. Nair and Meah are employees of Humana, which received funding to complete this research. Siadaty was an employee of Humana at the time of this study.

Treatments of Calcium Channel Blocker Overdose

Pharmaceutical agents are the most common causes of poisoning in Korea. Calcium channel blockers (CCBs) are commonly used in Korea for the management of hypertension and other cardiovascular diseases, but are associated with a risk of mortality due to overdose. Due to the frequent fatalities associated with CCB overdose, it is essential that the emergency physician is capable of identifying CCB intoxication, and has the knowledge to manage CCB overdose. This article reviews the existing clinical guidelines, retrospective studies, and systematic reviews on the emergency management of CCB overdose. The following are the varied treatments of CCB overdose currently administered. 1) For asymptomatic patients: observation with enough time and decontamination, if indicated. 2) For symptomatic patients: infusion of calcium salt, high dose insulin therapy, and vasopressor (norepinephrine) or atropine for bradycardia. 3) For patients refractory to the first line therapy or with refractory shock or impending arrest: lipid emulsion therapy and extracorporeal membrane oxygenation. 4) As adjunct therapy: phosphodiesterase inhibitors, glucagon, methylene blue, pacemaker for AV block. Small CCB ingestion is known to be fatal for pediatric patients. Hence, close observation for sufficient time is required.

SUN-697 Importance of Immunosuppressive Therapy for Managing Insulin Resistance Type B

Background: Autoimmune Antibodies against insulin receptors leading to refractory hyperglycemia is known as Type B insulin resistance. In addition to insulin management, immunosuppressive therapy appears to be an essential part for successful management. Clinical Case: A 20 year old African American woman with no significant past medical history presented to the Emergency Department with worsening nausea and vomiting for 5 days and shortness of breath. She admitted to polyuria, unintentional weight loss of 15 pounds in the last six months, decreased appetite, and hyper-pigmented rashes mostly on her back. The patient was not on any medications at home. No known drug allergies, no past surgical history. Family history was significant for Grandmother with Type 2 Diabetes Mellitus and Lupus on father’s side of family. The patient denied use of alcohol, tobacco, illicit and IV drug use. T: 37.2 °C, HR: 124, RR: 25, BP: 105/74, SpO2: 100%. Weight 45kg. Physical exam significant for Tachycardia but normal rhythm. Initial work up revealed new onset diabetes HbA1c 9.6% and massive pericardial effusion on echocardiogram s/p pericardiocentesis. Due to developing complaints of intermittent cyanosis of fingertips and intermittent joint pain of fingers, Rheumatology work up was ordered and positive for mixed connective tissue disease. Patient was treated with Cellcept 1500 mg BID, Plaquenil Sulfate 300 mg daily, and prednisone 12.5 mg BID. Hospital course was complicated due to hyperglycemia in 300s-400mg/dL requiring high amounts of insulin. Diabetes work up was negative for GAd-65 and islet cell antibodies. C-peptide was elevated at 16.1 ng/mL (0.8-3.1 ng/mL) and anti-Insulin an antibodies was 20uU/mL. Patient was euthyroid. Hyperglycemia persisted despite increasing doses of long and short acting insulin subcutaneously. The patient eventually required Insulin intravenously at 50 units/hour plus 50 units of short acting Insulin every 4 hours subcutaneously. The patient was transferred to a facility to begin Combined Immunosuppressive Therapy plus insulin to manage hyperglycemia due to insulin resistance. After six months of rituximab, high-dose pulsed steroids, cyclophosphamide, plus insulin therapy, glycemic index improved with HbA1c reduced to 5.6%. Conclusion: Combined Immunosuppressive Therapy in addition to insulin management of refractory hyperglycemia due to type B insulin resistance has been shown to not only be effective in controlling refractory hyperglycemia but preventing against recurrences as well. Reference: 1) Klubo-Gwiezdzinska J, Lange M, Cochran E, Semple RK, Gewert C, Brown RJ, Gorden P. Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study. Diabetes Care. 2018 Nov;41(11):2353-2360.

VERAPAMIL OVERDOSE: BALANCING PHYSIOLOGY OF DYNAMIC LVOTO WITH COMPLETE HEART BLOCK AND VASOPLEGIC SHOCK

Verapamil toxicity treatment varies based on severity of symptoms including use of gastric decontamination, IV calcium, glucagon, catecholamines for vasoplegic shock (VS), lipid emulsion, high dose insulin therapy and need for pacer for high grade AV block. A 57-year-old woman with depression and

Methylene blue in the management of severe distributive shock in calcium channel blocker overdose

Introduction: Deliberate polypharmacy overdose is associated with an increasing proportion of admissions to the intensive care unit. Overdose on hemodynamic active substances such as calcium channel blockers can be fatal as it is associated with severe distributive shock. Methylene blue has drawn attention in critical care medicine for its use in the management of distributive shock, particularly in cases of anaphylaxis, septic shock, and shock following cardiac bypass surgery. We describe the use of methylene blue in the management of refractory shock due to calcium channel blocker (CCB) overdose. Case Report: We present a case of benzothiazepine type CCB overdose which leads to admission to the intensive care unit for the management of severe distributive shock. Conventional treatments including vasopressors and high dose insulin therapy were instituted, but despite these treatments the patient remained hypotensive. The decision was made to administer methylene blue following which the patient achieved hemodynamic stability and was successfully weaned off all vasopressors. Conclusion: This case report specifically focuses on the use of methylene blue in distributive shock secondary to CCB overdose. Currently there are no randomized control trials to support its use, and evidence is limited to observational studies including single case reports. In this case report we describe the mechanism of action of methylene blue and why we believe it makes for the perfect adjunct therapy in calcium channel blocker overdose.