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Inadvertent Sulfonylurea Overdose and treatment with Octreotide: A Case Report
Authored by Sameed Qureshi
The most common complication of
sulfonylurea overdose is hypoglycemia [1]. The toxicity is caused secondary to
the exertion of the sulfonylurea pharmacological properties. It reduces the
glucose level by release of insulin from beta cells of the pancreas [2]. Early
symptoms of hypoglycemia from sulfonylureas are characterized by weakness,
hunger, diaphoresis, pallor, palpitations, sinus tachycardia, headache,
irritability, and tremor. If hypoglycemia remains untreated, neuroglycopenia
may develop resulting in impaired concentration and judgment, confusion,
blurred vision, drowsiness, and amnesia. Further progression can result in
seizures or coma, and possibly death [3].
Conventional therapy of
hypoglycemia with intravenous dextrose infusions may only temporarily correct
blood sugar levels as sulfonylurea and active metabolite levels may remain high
for a prolonged period resulting in persistent hypoglycemia [4]. Although
octreotide use has been advocated as a first line therapy, indications and
dosing are not firmly established. It has also been identified that the use of
octreotide may reduce the incidence of recurrent hypoglycemia that is seen with
dextrose-alone therapy. Our case report discusses a patient with severe
hypoglycemia resulting from suicide attempt by ingesting 24mg of glimepiride
and highlights the response to treatment with octreotide after failed attempts
to correct the patient’s hypoglycemia with dextrose.
Case Report
A fifty-eight-old male with no
previous co-morbidities was presented to was presented to the emergency room of
Northwest General Hospital, Peshawar in the month of January 2019. The son
reported that the patient is a non-diabetic. He ingested his spouse’s 12
tablets of 2mg glimepiride as a suicide attempt. In the emergency room, the
patient was tachycardic, tachypneic and diaphoretic. Initial glucose meter
reading was found to be 36mg/dL and a blood glucose level on the metabolic
panel was 49mg/dL. Patient serum creatinine was 2.1mg/dL. While in the
emergency room, the patient received 50% dextrose intravenously eventually
requiring an intravenous infusion of 10% dextrose. Despite this treatment, the
patient remained persistently hypoglycemic with blood sugars less than 80mg/dL.
He was admitted to the medical intensive care unit for close monitoring.
Despite giving high dose of
dextrose infusion, his blood sugars remained low. A decision was made at this
point to administer 50 micrograms of octreotide subcutaneously. Two hours
later, the patient’s blood sugar started to improve, and the intravenous 10%
dextrose was discontinued. Eight hours later, the patient received another dose
of 50 micrograms of octreotide and his blood sugars started improving. The dose
was continued for two days and he remained consistently euglycemia.
Once stable, his insulin levels
and C-peptide levels were done which were normal. Other parameters including
complete blood picture, U&Es, liver function tests and urine analysis were
within normal limit. Following initial correction of his low blood sugar, the
patient was encouraged orally. Once stable he was discharged on normal blood
sugars with advice to see a psychiatrist.
Discussion
Glimepiride is a second-generation
sulfonylurea indicated for diabetes mellitus type 2. After the intake, the drug
is completely absorbed, and the maximum concentration is reached in 0.7-2.8 h.
It is primarily metabolized in the liver, first to its active metabolite via
the cytochrome P450 and then to its dehydrogenated inactive metabolite [5].
Glimepiride was generally associated with lower risk of hypoglycemia compared
to other sulfonylureas and it should be used in caution with hepatic and renal
disease. It has a narrow therapeutic index. Glimepiride overdose is associated
with hypoglycemia [1]. Onset of hypoglycemia may be delayed up to 12h, and
duration may be prolonged for days after overdoses. Patients who are
hypoglycemic experience dizziness, weakness, headache, confusion, lethargy,
slurred speech, coma, and seizures. Other clinical effects include tachycardia,
palpitations, nausea, and diaphoresis. Protracted hypoglycemia can result in
death [2].
Several case reports are published
on sulfonylurea overdose in adults. Potential for hypoglycemia associated with
dosage increases is well described, especially in older patients, sometimes
with fatal outcomes. Review of national poison center data found 14
sulfonylurea-associated fatalities reported between 1992 and 1996 in adults
aged 18 to 79 years. Eleven cases were the result of suicides and involved
contestants [6].
A potential complication of
treatment of sulfonylurea-induced hypoglycemia with intravenous dextrose is
recurrent hypoglycemia. Dextrose administration results in hyperglycemia which
in turn potentiates insulin release from the pancreas leading to recurrent
hypoglycemia. Re-administration of dextrose perpetuates this cycle, resulting
in high dextrose requirements and the need for frequent monitoring of blood
glucose levels.
By contrast, octreotide, a
synthetic octapeptide analogue of somatostatin, effectively suppresses insulin
secretion and has a very benign adverse effect profile. The long-acting,
synthetic somatostatin analog, octreotide, is FDA-approved for the treatment of
acromegaly, metastatic carcinoid symptoms, and vasoactive intestinal secreting
tumors. It has also been used for the cessation of upper gastrointestinal
bleeding and to correct refractory hypoglycemia caused by sulfonylurea
overdoses. Octreotide can be administered either intravenously or
subcutaneously, with both routes having equivalent bioavailability. It appears
to abolish the need for hypertonic dextrose infusion, thus avoiding the need
for a central line, close observation, and complications relating to fluid and
electrolyte disturbances. This obviates the need for prolonged ICU admission.
Octreotide is now regarded as a first line antidote for sulfonylurea poisoning
with the role of dextrose confined to rapid restoration of euglycemia in the
already hypoglycemic patient and maintenance of euglycemia until such time as
octreotide can be sourced and administered [7].
Patients who developed
hypoglycemia with therapeutic doses of sulfonylureas have been given supplemental
dextrose and octreotide, with subsequent correction of the hypoglycemia. There
are numerous case reports describing treatment of sulfonylurea overdoses with
octreotide. In 2002, Carr and Zed described glyburide overdoses in two patients
with refractory hypoglycemia despite dextrose 50% boluses and 10% infusions who
demonstrated fewer hypoglycemic episodes and lower dextrose requirements with
octreotide 50μg every 8h for three doses. These authors provide a summary of
six previously reported cases that demonstrate the benefits of octreotide
therapy [8]. Subsequent to Carr and Zed’s report, there have been 13 case
reports on the treatment of sulfonylurea-induced hypoglycemia with octreotide,
including two cases in young children [9].
As octreotide represents the
definitive management of sulfonylurea induced hypoglycemia, efforts should be
made to administer it as soon as possible. If available in the remote area, it
can be safely commenced according the administration regime described above. If
not immediately available, efforts should be made to move the antidote to the
patient as part of the management plan
To read more about this article: https://irispublishers.com/ctcms/fulltext/inadvertent-sulfonylurea-overdose-and-treatment-with-octreotide-a-case-report.ID.000509.php
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