Effects of perioperative dextrose infusion on preventing postoperative nausea and vomiting in patients undergoing laparoscopic surgery: a meta-analysis of randomized controlled trials

Objective The aim of this study was to systematically examine the literature and assess the effects of perioperative dextrose infusion on the prevention of postoperative nausea and vomiting (PONV) in patients following laparoscopic surgery under general anesthesia. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Studies were eligible for inclusion if they evaluated the prevention of PONV with perioperative intravenous dextrose. Studies listed in PUBMED, Web of Science, and EMBASE databases published up to December 2020 were identified. Data were extracted and analyzed independently using a fixed-effects or random-effects model according to the heterogeneity. Results Six RCTs involving 526 patients were included. Our results showed that perioperative dextrose infusion not only reduced the incidence of PONV (risk ratio [RR] = 0.61, 95% confidence interval [CI]: 0.39–0.95; I2 = 59%) but also decreased the requirement for antiemetics compared with the control (RR = 0.53, 95% CI: 0.42–0.66; I2 = 32%). Furthermore, perioperative glucose infusion did not increase blood glucose levels compared with the control (mean difference [95% CI] = 74.55 [−20.64 to 169.73] mg/dL; I2 = 100%). Conclusion Our study reveals that perioperative dextrose infusion may reduce the risk of PONV after laparoscopic surgery. However, additional population-based RCTs are needed to confirm this finding.

A Case of Paraneoplastic Hypoglycemia From Squamous Cell Carcinoma of Undetermined Primary

Case: A 57 year old man with squamous cell carcinoma (SCC) of the tongue with complete response to chemoradiation was found unresponsive with a reading of “low” by a POC glucometer. He was treated with an IV dextrose bolus but had recurrent hypoglycemia requiring a continuous dextrose infusion. He was diagnosed with COVID-19 pneumonia, acute hepatitis (elevated liver enzymes), and acute kidney injury (elevated serum creatinine 1.2 mg/dL). Other labs: elevated TSH 8.44 uIU/mL, normal AM cortisol 16.4 ug/dl. A 5.1 cm mass was discovered in the left lung with bilateral nodules, biopsi revealed SCC of unclear origin (either lung or metastatic disease from prior tongue cancer). He was malnourished from prior cancer related dysphagia and nutritional supplements were added. Despite this and improvement in liver and kidney function, he had persistent hypoglycemia. He became hypoglycemic within 4-hrs while performing a 72-hr fast with labs: serum glucose 45 mg/dL, insulin &lt 2 uU/mL, c-peptide &lt 0.1 ng/mL, proinsulin &lt 4 pmol/L, beta hydroxybutyrate 0.17 mmol/L, IGF1 &lt 16 ng/mL (ref: 50 - 317), IGF2 147 ng/mL (ref: 267-616), negative hypoglycemia panel and insulin antibody. This was consistent with a paraneoplastic hypoglycemia known as non-islet cell tumor hypoglycemia (NICTH). To discontinue the dextrose infusion, he was started on prednisone 20 mg daily titrated up to 60 mg daily, intermittent tube feeds and palliative chemotherapy. With this, hypoglycemia improved, and the dextrose infusion was discontinued. Unfortunately, he had ischemic bowel perforation leading to cardiac arrest and death. Discussion: Our patient had NICTH as suggested by the 72-hr fast (non-insulin mediated hypoglycemia, IGF2/IG1 ratio &gt 10) and the presence of a tumor. It is mediated by tumor-produced IGF-2 causing increased glucose utilization, decreased gluconeogenesis, glycogenolysis and ketogenesis. Curiously, IGF-2 may not be elevated if the tumor produces a partially processed “big IGF-2” for which there is no commercial assay. Instead, an IGF2/IGF1 ratio close to or more 10 is indicative of NICTH. Mesenchymal and hepatic tumors are the most common cause of this rare entity with an incidence of one per million people years. A literature search showed very few reports of SCC-mediated-NICTH, with one case of esophageal SCC. Our patients’ primary tumor was undetermined (lung vs tongue) - but in either case this could be a novel association. A multidisciplinary approach is required centered around the tumor (surgery, chemotherapy, or radiation). High dose prednisone 30 to 60 mg daily can be used in the interim as it decreases IGF-2 but is not always successful. Recombinant hGH and glucagon are alternatives or can be combined with steroids. In summary IGF2/IGF1 ratio should be calculated, palliative tumor directed therapy should be initiated with prednisone and supplemental nutrition as adjuncts.

An Atypical Presentation of a Patient With Postprandial Hypoglycemic Induced Seizures

Background: Insulinomas are exceptionally uncommon pancreatic islet cell neuroendocrine tumors. Typically, insulinoma induced hypoglycemia occurs exclusively in the fasting state in 73 percent, reported in a retrospective analysis of 237 patients, whereas 6 percent reported only postprandial symptoms. Clinical Case: A 53-year-old female with a history of rheumatoid arthritis, obesity, and prediabetes initially admitted for new onset seizures and recurrent spontaneous hypoglycemic episodes. She experienced recurrent, symptomatic, post-prandial, hypoglycemia daily for the past 8 years. Each episode was closely associated with a high carbohydrate meal, inducing a post-prandial hypoglycemia more consistently and more profoundly than intermittent fasting. Symptoms of lightheadedness, shakiness, and seizure were exacerbated by each carbohydrate meal. Initial labs revealed serum glucose of 35 mg/dl. After recovery with dextrose infusion, a brief fasting trial less than 24 hours was performed with no recurrence of hypoglycemia. However, a mixed meal study utilizing watermelon resulted in a postprandial serum hypoglycemia of 28 mg/dl, provoking a seizure within 30 minutes. During her hospitalization, recurrent hypoglycemia was found during the postprandial period rather than intermittent fasting periods requiring dextrose infusion and octreotide. A Hypoglycemia panel sent during the initial episode was consistent with endogenous hyperinsulinism (Serum glucose=35, Insulin level=24, Proinsulin=166, C-peptide=0.9, BHB=undetectable, Sulfonurea=negative). A subsequent CT of the abdomen/pelvis revealed a mass associated with the pancreatic tail, measuring 4.1 x 4.4 x 5.2 cm concerning for pancreatic malignancy. A fine needle aspiration followed by a distal pancreatectomy and splenectomy with histopathological and immuno-histochemical evaluation confirming a well differentiated (grade 1), 5.0 x 4.5 x 3.0 cm, neuroendocrine tumor (insulinoma). Her recovery, post-operatively, was complicated by an intraabdominal abscess, left pleural effusion, necessitating insulin therapy for hyperglycemia believed to be secondary to morbid obesity, weight gain, and insulin resistance. Hypoglycemic symptoms resolved, blood glucose normalized, and insulin therapy was weaned over the following 3 months and she remains on metformin to date with no evidence of recurrence. Conclusion: Although rare, an insulinoma should be considered in the differential diagnosis of any individual with recurrent episodes of frequent symptomatic hypoglycemia. The classical clinical manifestation of an insulinoma is a fasting hypoglycemia, with distinct episodes of autonomic symptoms. However, postprandial symptoms have been reported with increasing frequency. Here we present a case of surgically confirmed insulinoma with predominantly post-prandial hypoglycemia.

Physiologic Effects of Exogenous Dextrose in Murine Klebsiella pneumoniae Sepsis Vary by Route of Provision

Sepsis is characterized by a dysregulated immune response to infection. Nutrition is important in the care of septic patients, but the effects of specific nutrients on inflammation in sepsis are not well defined. Our prior work has shown benefits from early enteral dextrose infusion in a preclinical endotoxemia model of sepsis. In the current study, we extend our initial work to examine the effects of dextrose infusions, varying by route of administration, on inflammation and glycemic control in a more clinically relevant and translational model of Klebsiella pneumoniae (KP) bacteremia. Ten-week old C57BL6/J male mice (n = 31) underwent the implantation of indwelling vascular catheters, followed by inoculation with oropharyngeal KP. The mice were randomized 24 h after inoculation to (1) intravenous (IV) dextrose, (2) enteral dextrose, or (3) enteral saline (control) to study the effects on systemic inflammation, hemodynamics, and glycemic control. At 72 h, 77% of the control mice died, whereas IV dextrose induced 100% mortality, associated with increased inflammation, hyperglycemia, and hypotension. Enteral dextrose reduced mortality to 27%, promoted euglycemia, and reduced inflammation compared to IV dextrose. We conclude, in a bacteremic model of sepsis, that enteral (but not IV) dextrose administration is protective, suggesting that the route of nutrient support influences inflammation in sepsis.

SUN-698 Management of Hyperglycemia in an Adult Patient with Glycogen Storage Disease Type 1b

Background: Glycogen storage disease type 1b (GSD1b) is caused by a deficiency of glucose 6 phosphatase leading to glycogen deposition. The hallmark findings of GSD1b are hypoglycemia and lactic acidosis. GSD1b can be associated with hepatomegaly, hypertriglyceridemia, hematologic abnormalities, hypothyroidism, inflammatory bowel disease, proteinuria, and hypoglycemic seizures. Main stay of therapy is to avoid fasting and to ingest frequent feeds high in complex CHO. Raw cornstarch (CS) has been used for the treatment of hypoglycemia in GSD1b since the early 1980s. CS is digested slowly, providing a steady release of glucose allowing for more stable glucose levels over a longer period of time as compared with other sources of CHO. Adults may require more CS to maintain BG >70 mg/dL and lactate <2mmol/L during the night. We report a case of an adult patient with GSD1b admitted with inability to tolerate oral intake and found to have persistent hyperglycemia on admission requiring insulin therapy. Clinical Case: A 31 year old female with a history of GSD1b complicated by hypoglycemia, Crohn’s disease, chronic pancreatitis and neutropenia was admitted for abdominal pain, emesis and inability to tolerate CS. She was made NPO and was started on a dextrose drip to avoid hypoglycemia and hyperlactatemia. The rate of dextrose infusion was adjusted to maintain lactate levels <2 mmol/L. She developed persistent hyperglycemia with glucose values of 250–350 mg/dL. Laboratory evaluation revealed an HbA1c of 7.6% (reference [ref] 4.3–5.6%), C-peptide of 1.3 ng/mL (ref 0.8–3.9 ng/mL), lactate of 2.3–3.1 mmol/L (ref 0.5–2.2 mmol/L). BHB levels were normal (WNL). Anti-GAD, insulin and islet cell antibodies were negative. The main goal was to avoid hypoglycemia while keeping ketone and lactate levels WNL. The decision was made to start a regular insulin infusion at a constant rate of 1 u/hr to keep BG <180 mg/dL while on the dextrose infusion with close monitoring of lactate and BHB. Insulin and dextrose drip rates were adjusted based on BG. The ultimate goal was to determine total daily insulin requirements while ingesting her home CS doses and to transition to long acting insulin. Short acting insulin boluses were not used given risk of hypoglycemia. The patient’s unpredictable tolerance to CS made determining a fixed insulin dose challenging. She eventually managed to tolerate CS and was transitioned to 10 units of insulin Detemir twice daily. She was discharged with plans to get a CGM and a ketone meter. BG readings at home were between 140–170 mg/dL. Conclusion: We report a rare case of GSD1b and diabetes. The pathogenesis may be related to effects of chronic pancreatitis or metabolic syndrome. Treatment of hyperglycemia in patients with GSD1b is challenging given the heightened risk of fasting hypoglycemia. Treatment options are limited, and there are no data regarding the safe use of insulin in this patient population.

SAT-117 Refractory Paraneoplastic Non Islet Cell Tumor Hypoglycemia (NICTH) from Hepatocellular Carcinoma Managed with Somatostatin Analogue and Glucocorticoids

Non islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome generally seen in tumors of mesenchymal and hepatic origin. This syndrome is characterized by life threatening hypoglycemia caused by over expression of high molecular weight insulin-like growth factor 2 (IGF 2). The main stay of treatment is surgical resection of the tumor with no clear medical management being reported as standard of care. We present the case of a 72 year old Cambodian man with no history of diabetes mellitus who presented to our institution with severe hypoglycemia complicated by a seizure and was found to have hepatocellular carcinoma (HCC). Hypoglycemia occurred during times of fasting. Laboratory evaluation revealed a serum glucose of 30mg/dl with insulin level of 2.2 mcIU/mL [2.6 - 24.9 mcIU/ml], C-Peptide of 0.17 ng/mL [0.80 - 3.85 ng/ml], BHB <0.1 mmol/L [0.0 - 0.3 mmol/L] and Proinsulin of <0.4 pmol/L [< or = 18.8 pmol/L]. Hypoglycemic agents screening was negative. Insulin Antibody was negative <0.4 U/mL [<0.4 U/mL] and adrenal insufficiency and hypothyroidism was ruled out. Patient was found to have an elevated IGF 2: IGF 1 ratio of 78 confirming the diagnosis of NICTH. IGF 2 level was 780 ng/ml [333 - 967 ng/ml] while IGF-1 was < 10 ng/ml [32-200 ng/ml] He was not a candidate for surgery due to portal vein involvement and tumor radioembolization was unsuccessful. Despite Prednisone dose of 10 mg twice daily and frequent complex carbohydrate meals, he still continued to have hypoglycemia ultimately requiring hospitalization. During hospitalization, he was treated with 50% dextrose infusion, 37.5 grams of dextrose gel every three hours and frequent small meals. Hypoglycemia remained refractory and a trial of diazoxide was ineffective. He was then started on octreotide with titration to 100mg every 8 hours with significant reduction in hypoglycemic episodes. He continues to remain on octreotide, Prednisolone 20mg twice a day, dextrose gel and dextrose infusion. Goal is to wean dextrose infusion and transition him to Pasireotide 40mg monthly. Hepatocellular carcinoma has been associated with NICTH in the literature. NICTH is characterized by an IGF2:IGF1 ratio >10 as there is no commercially available assay for big IGF II. Definitive treatment involves surgical resection or tumor debulking. Octreotide has antiangiogenic and antineoplastic properties and unfortunately, few studies have shown improved survival and quality of life in patients with advanced HCC. In the case of our patient, tumor was unresectable and NICTH improved with octreotide and prednisolone.

Glucose related endocrine and metabolic responses following bolus intravenous hypertonic dextrose administration in Iranian fat-tailed ewes at different pre and post parturition periods

Providing glucose as primary metabolic fuel for maintenance, foetal growth and milk production may be considered necessary for protection against negative energy balance and metabolic disorders. Five adult Ghezel ewes were selected 4 weeks before their parturition and followed at 2 weeks before, 2 and 4 weeks and 2, 3 and 4 months after parturition. Dextrose 50% was administered at 500 mg/kg, 10 mL/kg/hour, and blood samples were collected from all ewes prior to and 1, 2, 3 and 4 hours after 50% dextrose infusion. Serum levels of glucose, beta-hydroxybutyric acid, non-esterified fatty acids, cholesterol, triglyceride, high, low and very low density lipoproteins, insulin, triiodothyronine, thyroxine, prolactin, cortisol and insulin like growth factor-1 were evaluated. Glucose and insulin were increased significantly and immediately following intravenous dextrose administration at all studied periods. The levels of beta-hydroxybutyric acid and non-esterified fatty acids were significantly decreased following dextrose infusion at all periods. Triiodothyronine was decreased in pregnant ewes and increased in non-pregnant, lactating ones. The significant increasing cortisol patterns were detected at 2 and 4 weeks before and 2 and 4 weeks after parturition following dextrose administrations. The decreasing patterns of insulin like growth factor-1 were seen in all studied periods. Prolactin was significantly increased following dextrose administration at 4 and 2 weeks before and 2 weeks after parturition. Bolus intravenous hypertonic dextrose administration could induce the obvious endocrine and metabolic responses in Ghezel ewes via providing a source of energy and the glucose is an important direct controller of metabolic interactions in Ghezel ewes.