Treatment of sulfonylurea and insulin overdose.

The most common toxicity associated with sulfonylureas and insulin is hypoglycaemia. The article reviews existing evidence to better guide hypoglycaemia management. Sulfonylureas and insulin have narrow therapeutic indices. Small doses can cause hypoglycaemia, which may be delayed and persistent. All children and adults with intentional overdoses need to be referred for medical assessment and treatment. Unintentional supratherapeutic ingestions can be initially managed at home but if symptomatic or if there is persistent hypoglycaemia require medical referral. Patients often require intensive care and prolonged observation periods. Blood glucose concentrations should be assessed frequently. Asymptomatic children with unintentional sulfonylurea ingestions should be observed for 12 h, except if this would lead to discharge at night when they should be kept until the morning. Prophylactic intravenous dextrose is not recommended. The goal of therapy is to restore and maintain euglycaemia for the duration of the drug's toxic effect. Enteral feeding is recommended in patients who are alert and able to tolerate oral intake. Once insulin or sulfonylurea-induced hypoglycaemia has developed, it should be initially treated with an intravenous dextrose bolus. Following this the mainstay of therapy for insulin-induced hypoglycaemia is intravenous dextrose infusion to maintain the blood glucose concentration between 5.5 and 11 mmol l(-1) . After sulfonylurea-induced hypoglycaemia is initially corrected with intravenous dextrose, the main treatment is octreotide which is administered to prevent insulin secretion and maintain euglycaemia. The observation period varies depending on drug, product formulation and dose. A general guideline is to observe for 12 h after discontinuation of intravenous dextrose and, if applicable, octreotide.

Myocardial Injury without Electrocardiographic Changes after a Suicide Attempt by an Overdose of Glimepiride and Zolpidem: A Case Report and Literature Review.

A 40-year-old diabetic man was admitted to our hospital for poor glycemic control. During hospitalization, he took 42 mg glimepiride and 50 mg zolpidem as a suicide attempt. The following day, the creatine kinase-MB fraction and troponin I levels were elevated to 112 IU/L and 8.77 ng/mL, respectively, without any electrocardiographic abnormalities. The patient recovered completely without any complications. Four weeks later, coronary computed tomography angiography and myocardial perfusion scintigraphy revealed moderate one-vessel coronary disease without the evidence of myocardial ischemia or old infarction. Cardiac-specific markers must be considered in sulfonylurea-induced hypoglycemic patients, particularly when the patient is unconscious and does not exhibit any clinical manifestations.

[Non usual cases of hypoglycaemia--hypoglycaemia factitia]. / Neobvyklé prípady hypoglykémie--hypoglycaemia factitia.

Hypoglycaemia factitia means also in recent time serious diagnostic and therapeutic problem in medical clinical practice, whereby often repeating episodes of serious hypoglycaemia in patients with diabetes mellitus, but also in patients without diabetes mellitus could be very difficult do resolve. First unsuccessful diagnosis implicit from wrong chose of examination algorithm, can lead to unidentified surgical interventions as are laparotomy and pancreatectomy, respectively. Hypoglycaemia factitia is considered to be one of many manifestations of so called Münchhausen's syndrome for that is typical acting of diabetic patient with goal to intentionally making hypoglycaemia or within suicidal attempt of patient on the basis psychological disease with intention to attract attention of surrounding community to himself due to application of insulin or sulfonylurea drugs. Diagnostic and therapeutic process could be in the case of hypoglycaemia factitia extremely difficult as from time side, than from health and also from economical side and that why necessary to approach with maximum responsibility.

Continuous octreotide infusion for sulfonylurea-induced hypoglycemia in a toddler.

BACKGROUND: Ingestion of a sulfonylurea by toddlers can cause profound hypoglycemia and neurologic sequelae. Although mild cases can be managed with dextrose and boluses of octreotide, optimal management of patients with severe hypoglycemia and cerebral injury has not been well established. OBJECTIVE: Our objective was to report the use of continuous infusion octreotide for tight glucose control after accidental sulfonylurea ingestion with severe neurologic dysfunction. CASE REPORT: A 17-month-old child presented to the emergency department with marked hypoglycemia, cerebral edema, and persistent seizures after ingestion of an unknown amount of glipizide. Hypoglycemia was refractory to i.v. dextrose bolus/infusion and subcutaneous octreotide. Continuous i.v. octreotide was utilized in conjunction with low-volume/high-concentration dextrose infusion as treatment, allowing for tight glucose and fluid management in the setting of cerebral edema. CONCLUSIONS: Continuous infusion of octreotide resulted in rapid stabilization of blood glucose levels while maintaining fluid-restriction goals. Our patient demonstrated reversibility of diffuse cerebral edema in this setting with near complete recovery of neurologic function. Octreotide administration by continuous infusion may be preferable to subcutaneous bolus administration for the treatment of severe sulfonylurea-induced hypoglycemia with associated neurologic injury.

Evaluation of the use and safety of octreotide as antidotal therapy for sulfonylurea overdose in children.

OBJECTIVES: The objectives of this study were to evaluate the effect of octreotide on number of hypoglycemic episodes and blood glucose concentrations (BGCs) in a case series of young children who received octreotide for treatment of sulfonylurea-induced hypoglycemia and to identify the frequency of adverse effects associated with octreotide's use for this indication. METHODS: A retrospective review of 9 years of National Poison Data System pediatric sulfonylurea overdoses treated with octreotide was conducted. Inclusion criteria were age younger than 6 years with acute sulfonylurea overdose managed in a health care facility. Redacted poison center charts were obtained, and data on pretreatment and posttreatment number of hypoglycemic episodes and BGCs as well as medical outcomes and adverse reactions were extracted and analyzed. RESULTS: There were 121 octreotide cases. Patients experienced a median of 2.0 and 0.0 hypoglycemic episodes before and after treatment, respectively (P < 0.0001). The median lowest BGC was significantly higher after octreotide administration (P < 0.001). In 73% of children, only 1 dose of octreotide was given. Hyperglycemia was noted in 3 children who also received dextrose in whom adverse effects to therapy were coded. CONCLUSIONS: Octreotide administration decreases number of hypoglycemic events and increases BGCs. The majority of children who receive octreotide require only 1 dose. There were no adverse effects documented in these children who received octreotide as an antidote for sulfonylurea-induced hypoglycemia.

Octreotide for the treatment of sulfonylurea poisoning.

BACKGROUND: Sulfonylureas are used extensively for treating type-2 diabetes mellitus. Sulfonylurea poisoning can produce sustained and profound hypoglycemia refractory to IV dextrose, particularly in children and the elderly. OBJECTIVE: To review the use of octreotide, a long-acting somatostatin analog, in the treatment of sulfonylurea-induced hypoglycemia. METHODS: A computerized search of U.S. National Academy of Medicine, Embase, PubMed and Toxline databases was undertaken using the keywords "octreotide", "sulfonylurea", "poisoning", "intoxication", "overdose" and "children". Textbooks of Clinical Toxicology and Pharmacology and the articles cited in their bibliographies were also searched. Twenty-four publications (19 articles and five conference abstracts) were identified; no publication was excluded. PHARMACOLOGY OF OCTREOTIDE: Octreotide, a synthetic peptide analog of somatostatin, binds to G protein-coupled somatostatin-2 receptors in pancreatic beta-cells, resulting in decreased calcium influx and inhibition of insulin secretion. Octreotide markedly inhibited insulin secretion and decreased the number of hypoglycemic events and supplemental dextrose requirements in animal studies. In humans octreotide markedly inhibited insulin release, increased serum glucose concentration, reduced dextrose requirement, prevented recurrent hypoglycemia and was superior to IV dextrose and diazoxide after administration of sulfonylureas. EFFICACY OF OCTREOTIDE IN PEDIATRIC SULFONYLUREA POISONING: Fourteen pediatric patients were reported; 13 ingested second-generation sulfonylureas, with time to hypoglycemia of 1.5-16 hours. IV dextrose (10-25%) was administered before and after octreotide therapy. Octreotide was given after failure to correct hypoglycemia with IV dextrose in doses of 0.51-2 µg/kg IV or SC; two also required an IV octreotide infusion. Seven patients (50%) had recurrent hypoglycemia and received IV dextrose and additional octreotide. EFFICACY OF OCTREOTIDE IN ADULT SULFONYLUREA POISONING: Fifty-three patients were reported in prospective controlled (n = 22) and retrospective (n = 9) studies, case series (n = 6) and case reports. Fifty-one ingested second-generation sulfonylureas with time to hypoglycemia of 1-13 hours. All received IV dextrose (10-50%) before and after octreotide treatment. Octreotide 40-100 µg SC or IV was administered followed by additional doses in most patients; three patients also required an IV infusion. Octreotide significantly increased serum glucose concentrations, decreased dextrose requirement and recurrent hypoglycemic events compared with IV dextrose. Recurrent hypoglycemia was recorded in 22-50% of the patients treated with octreotide. THERAPEUTIC RECOMMENDATIONS: Based on the published clinical and pharmacokinetic data of sulfonylureas and octreotide, we suggest the following dose regimens: in children, octreotide 1-1.5 µg/kg IV or SC, followed by 2-3 more doses 6 hours apart. In adults, octreotide 50 µg SC or IV, followed by three 50 µg doses every 6 hours. During this treatment IV dextrose infusion should be gradually tapered off. ADVERSE EVENTS: Hypertension and apnea were recorded in one pediatric patient 30 minutes after IV octreotide; the relationship to octreotide is unclear. One adult patient with chronic renal failure treated with atenolol developed severe hyperkalemia. CONCLUSIONS: Although relatively limited, the available data suggest that octreotide should be considered first-line therapy in both pediatric and adult sulfonylurea poisoning with clinical and laboratory evidence of hypoglycemia. Maintenance doses of octreotide may be required to prevent recurrent hypoglycemia.

Hypoglycemia after accidental pediatric sulfonylurea ingestions.

BACKGROUND: Because the prevalence of type 2 diabetes increases annually, there has been an increase in pediatric exposures to sulfonylureas. These medications are associated with delayed and often prolonged hypoglycemia. As such, most authorities but not all recommend admission for all pediatric patients with an accidental sulfonylurea ingestion. METHODS: This study is a retrospective chart review of all pediatric patients with sulfonylurea exposures admitted for 9 years at an urban, pediatric teaching hospital. The incidence and characteristics of the hypoglycemia were recorded and analyzed. RESULTS: During this time span, 93 patients with accidental sulfonylurea exposures were admitted, with a median age of 1.83 years. Glyburide and glipizide accounted for most sulfonylureas. Hypoglycemia (blood glucose level <50 mg/dL) developed in 25 (58.1%) of 43 patients who ingested glipizide, compared with 10 (25.6%) of 39 patients who ingested glyburide. The overall incidence of hypoglycemia was 44%. Hypoglycemia was more likely to occur with glipizide ingestion than glyburide (odds ratio, 3.89 [95% confidence interval, 1.51-9.98]). No patient with a known time of ingestion developed hypoglycemia after 13 hours. CONCLUSIONS: Hypoglycemia is common after accidental sulfonylurea exposures. The results of this study support mandatory admission to a monitored setting for at least 16 hours, with frequent glucose determinations.

Hypoglycemia in pediatric sulfonylurea poisoning: an 8-year poison center retrospective study.

OBJECTIVE: The goal of this study was to describe the clinical effects and time of onset of hypoglycemia in pediatric sulfonylurea poisoning. METHODS: This was a retrospective, descriptive study of pediatric (<6 years old) sulfonylurea exposures with hypoglycemia (glucose concentration <60 mg/dL) that were consulted on by the California Poison Control System for the 8-year period between January 1, 2002, and December 31, 2009. RESULTS: Of the 1943 consultations for pediatric sulfonylurea exposure in the study period, 300 children developed hypoglycemia. Ten percent had hypoglycemia occurring or persisting ≥ 12 hours after ingestion despite receiving treatment. All 5 children with seizures experienced these before hospital presentation. The mean (SD) time to onset of hypoglycemia in children not given any prophylactic treatment was 2.0 (1.2) hours. The mean (SD) times in children receiving prophylactic food only, intravenous glucose only, and both food and intravenous glucose were 5.9 (3.9), 5.7 (2.5), and 8.9 (3.6) hours, respectively. Ranges were 1 to 18, 1.5 to 9, and 2.5 to 15 hours. Seven of 40 patients (18%) receiving prophylactic food only had an onset of hypoglycemia >8 hours after sulfonylurea ingestion. CONCLUSIONS: Pediatric sulfonylurea exposure can result in significant poisoning. Severe effects such as seizures occurred only in cases of unrecognized sulfonylurea ingestion. The onset of hypoglycemia after pediatric sulfonylurea ingestion can be delayed by as much as 18 hours by either free access to food or administration of intravenous glucose.

Octreotide's role in the management of sulfonylurea-induced hypoglycemia.

The objective is to evaluate the evidence regarding octreotide's efficacy as a treatment for sulfonylurea-induced hypoglycemia. A search of PubMed for articles published from 1965 to 2008 using combinations of the terms octreotide, antidote, sulfonylurea, overdose, poisoning, and toxicity was performed. References from identified articles were reviewed for additional sources. Animal studies, case reports, case series, and randomized controlled trials were evaluated. An animal model of sulfonylurea overdose demonstrates that octreotide reduces the number of refractory sulfonylurea-induced hypoglycemic episodes. Published case reports describe the use of octreotide to prevent recurrent hypoglycemia after sulfonylurea overdose. A retrospective case series demonstrates that administration of octreotide decreases the need for supplemental dextrose boluses as well as hypoglycemic events. Two prospective, controlled trials determined that octreotide and supplemental dextrose increase blood glucose concentrations with fewer hypoglycemic events. Based on animal and human data, there is sufficient evidence to recommend the use of octreotide with supplemental dextrose for the treatment of sulfonylurea-induced hypoglycemia.

Sulfonylurea intoxication at a tertiary care paediatric hospital.

BACKGROUND: Unintentional poisoning with sulfonylurea hypoglycaemic drugs is a serious danger to infants and children, as the ingestion of relatively small amounts can be fatal. Although the administration of octreotide is considered effective in patients that remain hypoglycaemic despite glucose administration, experience in children is limited. METHODS: A retrospective chart review of the clinical features of all children following sulfonylurea ingestion presenting between April 2001 and November 2008 at the Hospital for Sick Children in Toronto. RESULTS: Ten children were identified with sulfonylurea exposure; six were classified as suspected ingestion and four had confirmed signs of sulfonylurea overdoses (mean age: 8.2 years; range 1.5 - 15). All four patients with confirmed ingestion were exposed to glyburide and developed severe hypoglycaemia; two were toddlers and two teenagers. Ingestion was accidental in the case of the toddlers, and suicidal attempts in the case of the adolescents. All patients were initially treated with glucose infusions. Both toddlers also received octreotide with favourable response and no rebound hypoglyacemia. The two teenagers were treated only with prolonged glucose infusions; in both cases rebound hypoglycaemia and increased glucose requirements were observed. DISCUSSION: Glyburide-induced hypoglycaemia was pronounced in all patients identified. Treatment with octreotide proved effective in the 2 infants treated, agreeing with the limited experience reported to date in the literature, and suggesting that octreotide should be considered the treatment of choice in children.

Acute intentional self-poisoning with a herbicide product containing fenoxaprop-P-ethyl, ethoxysulfuron, and isoxadifen ethyl: a prospective observational study.

BACKGROUND: Herbicides are commonly ingested for self-harm, but relatively little has been published on poisoning with herbicides other than paraquat and glyphosate. We report here a case series of patients with acute exposure to a combination herbicide (brand name Tiller Gold or Whip Super) containing the selective phenoxy herbicide compounds fenoxaprop-P-ethyl and ethoxysulfuron and a safener isoxadifen ethyl. METHOD: Clinical data on all patients presenting with Tiller Gold or Whip Super poisoning to two General Hospitals in Sri Lanka from 2002-2008 were collected prospectively until discharge. RESULTS: Eighty-six patients with a history of Tiller Gold or Whip Super ingestion were included. The main clinical features were an epigastric burning sensation and vomiting; however, most of those who vomited had received gastric lavage or forced emesis. Eight patients had a reduced level of consciousness on admission (Glasgow coma scale 9-14) that resolved without intervention over several hours. Only symptomatic and supportive care was required. The median hospital stay was 1 day (IQR: 1-2) and the case fatality was zero (95% confidence interval: 0-4.2%). This low case fatality compared favorably with the case fatality of other common herbicides in our cohort: paraquat >40%, propanil >10%, 4-chloro-2-methylphenoxyacetic acid > 5%, and glyphosate >2%. CONCLUSION: This combination herbicide product appears to be safe in patients with acute self-poisoning, particularly in comparison with other herbicides, and causing few clinical features.

Intoxicaciones por antidiabéticos orales en España. Análisis y evolución a lo largo de 13 años (1991-2003) / Poisonings by oral antidiabetics drugs in Spain. Analysis and evolution during 13 years (1991-2003)

Introducción. La prevalencia de diabetes tipo 2aumenta y aumentará en los próximos años. El tratamiento farmacológico de la diabetes tipo 2 inicialmente son los antidiabéticos orales. El objetivo de nuestro estudio es conocer la existencia y evolución de las intoxicaciones por antidiabéticos orales en España, durante el período 1991-2003.Resultados. El número total de intoxicacionesfue de 309 sujetos, siendo más frecuentes en mujeres (52,9%) que en hombres (47,1%). Las intoxicaciones fueron clasificadas en asintomáticas el 13,9%, leves el 49,5%, moderadas el 31,3% y graves el 5,1%. El grupo farmacológico conmayor número de intoxicaciones fue el de lassulfonilureas 66,5%, y dentro de éste el grupo delas glibenclamidas. En los últimos años sepresentan intoxicaciones con más de un fármaco,presentándose en el año 2002 una intoxicación portriple terapia (sulfonilurea-biguanida y inhibidor dela alfa glucosidasa). Es importante destacar laausencia de mortalidad y la evolución de lasintoxicaciones, con un aumento del número decasos de metformina y disminución de losinhibidores de alfa-glucosidasa. En nuestro estudio,destacamos el mayor número de intoxicaciones enel grupo de lactantes y niños respecto a los adultos.Todo pone de manifiesto la importancia de uncentro de referencia para estudios epidemiológicos,la correcta prescripción y el riesgo cada vez mayordel colectivo de niños al aumentar la población dediabéticos, y con ella la prescripción de losantidiabéticos orales

Introduction. The prevalence of diabetes type 2increases and increased in the next years.The pharmacology treatment of the diabetestype 2 is the oral antidiabetic oral drugs. Theobjective of our study is to know the existence andevolution of the poisonings by oral antidiabeticsin Spain. We have studied the poisonings registeredby oral antidiabetics in the National System ofinformation toxicological, centre of nationalreference for acute poisonings in our country,during period 1991-2003.Results. The total number of poisonings was of309 subjects, being more frequent in women 52.9%versus 47.1% in men. The clinical poisonings wereclassified in asymptomatic 13.9%, low symptoms49.5% moderate serious 31.3% serious 5.1%. Thepharmacologic group with greater number ofpoisonings was of sulfonilurea 66.5%, within thisgroup the glyburide one. In the last years poisoningswith but of a drug appear appearing in the 2002poisoning by triple therapy (sulfonilurea-metforminand alpha-glucosidase inhibitor). It is important toemphasize the absence of mortality and themodification of prescription increase of casesof metformin and diminution of alpha-glucosidaseinhibitor. In our study we emphasized the greaterone I number of poisonings in group of sucklingbabies and children with respect to the adults.Everything shows the importance of the correctprescription and use of the oral antidiabetics

Octreotide in children with hypoglycaemia due to sulfonylurea ingestion.

Sulfonylureas are commonly prescribed for type 2 diabetes mellitus; however, overdose or accidental ingestion may result in profound and prolonged hypoglycaemia with permanent neurological sequelae and death. We describe two cases of children with hypoglycaemia due to presumed accidental ingestion of sulfonylureas, where traditional methods of raising blood sugar levels were unsatisfactory. Two studies describe Octreotide for adults with hypoglycaemia, but there are no studies examining the use of Octreotide in children for this indication. Given that Octreotide has been shown to be safe in children when used for other indications, we used Octreotide to safely restore euglycaemia.

Use of octreotide acetate to prevent rebound hypoglycaemia in sulfonylurea overdose.

A short cut review was carried out to establish whether octreotide can prevent rebound hypoglycaemia after sulfonylurea overdose. Fourteen papers were found using the reported searches, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are summarised in table 2. It is concluded that octreotide may be safe and effective in this situation.

Antidiabetic medications in overdose: a comparison of the inquiries made to a regional poisons unit regarding original sulfonylureas, biguanides and insulin.

OBJECTIVE: The drugs most commonly used to treat diabetes mellitus are sulfonylureas, biguanides and insulin. The most serious effects seen in overdose with these agents are hypoglycemia or lactic acidosis which may be fatal or cause cerebral defects. The present investigation analyzes inquiries made to a regional poisons unit involving overdoses with sulfonylureas, biguanides and insulin. PATIENTS AND METHODS: A total of 218,070 made inquiries between 1995 and 2004 were evaluated. The inquiries were received by telephone and a standardized questionnaire was sent subsequently to the physicians calling for follow-up information. The cases were analyzed with regard to gender, age, etiology, symptoms and clinical outcome. RESULTS: 263 inquiries concerning sulfonylureas (48.3% female, 49.4% male, 2.3% sex unknown, average age 39.1 +/- 26.8 years), 172 concerning biguanides (60.5% female, 37.2% male, 2.3% sex unknown, average age 41.5 +/- 24.1 years), and 191 concerning insulin (53.9% female, 41.9% male, 4.2% sex unknown, average age 44.6 +/- 16.7) were made. In cases involving sulfonylureas, the etiology was deliberate self-poisoning in 62.7% and accidental in 31.9% (biguanides 60.5% and 29.1%, insulin 85.3% and 9.4%). Using the Poisoning Severity Score, no symptoms were observed in 41.4% of the patients with sulfonylurea overdose (biguanides 40.1%, insulin 22.5%), minor symptoms in 37.6% (biguanides 32.6%, insulin 33.5%), major symptoms in 14.4% (biguanides 13.4%, insulin 26.2%) and serious symptoms in 4.6% (biguanides 12.2%, insulin 14.7%). Returned questionnaires reporting clinical outcomes showed that a full recovery occurred in most patients (sulfonylureas 97.4%, biguanides 93.0%, insulin 94.4%), cerebral defects persisted in 1.8% of the cases involving sulfonylureas (biguanides 1.5%, insulin 2.4%), and that 0.9% of the patients with sulfonylurea overdose died (biguanides 6.1%, insulin 3.6%). CONCLUSIONS: Sulfonylureas were the most frequently observed medication in cases of overdose with antidiabetic agents. Insulin overdose caused the highest number of major and serious symptoms. Overdose with biguanides led to the most deaths.