Authored by Sameed Qureshi
Suicide attempts using hypoglycemic agents are uncommon but are
associated with a high level of morbidity and mortality. A
fifty-eightyear-
old-gentleman with no history of diabetes was presented in a state of
shock to the emergency room with the ingestion of 12 tablets of 2mg
glimepiride. The patient was in persistent state of hypoglycemia. In
such cases of sulfonylurea toxicity, goal of therapy depends on the
adequate
glucose supplementation to maintain normal blood glucose level.
Octreotide is an effective drug in preventing rebound hypoglycemia after
sulfonylurea ingestion. Octreotide in combination with dextrose should
be considered for first-line therapy in the treatment of
sulfonylurea-induced
hypoglycemia.
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.
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.
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....Open access Journal of Clinical & Medical Sciences
Please follow the URL to access more information about this article
No comments:
Post a Comment