You Have A New Patient!
A 75-year-old woman was brought to the emergency department by her relatives for “not being her usual self” for the past day. Her relatives reported that the patient had not eaten much of her usual breakfast, as she was not feeling well. She was on insulin therapy for diabetes but was otherwise healthy, with no reported allergies. At triage, she appeared confused and disoriented. Her vital signs were as follows: HR 95/min, RR 18/min, BP 141/85 mmHg, T 37.7°C, and SpO₂ 99% on room air.
Given her past medical history, a capillary blood glucose test was performed at triage, which revealed a reading of 2.6 mmol/L (47 mg/dL). She was laid down and brought to an examination room on a stretcher.
What Do You Need To Know?
Importance
Hypoglycemia is a common medical emergency that is easily treatable but can be life-threatening if not addressed promptly. It is a frequent condition in patients with diabetes. Hypoglycemia can cause a variety of symptoms, including confusion, loss of consciousness, seizures, and even coma. These symptoms can be mistaken for other conditions, so it is important to recognize the signs of hypoglycemia and provide prompt treatment. Hypoglycemia can often be treated with oral glucose, but severe cases may require intravenous administration of glucose or other medications. Knowledge of appropriate treatments for hypoglycemia is crucial to prevent serious complications. Hypoglycemia may also occur in patients with other conditions, such as liver failure or sepsis. In these cases, it is also important to address the underlying condition [1].
Epidemiology
The epidemiology and incidence of hypoglycemia are difficult to study, as many patients experiencing hypoglycemic symptoms recognize and treat them without visiting the emergency department (ED). Hypoglycemia is more common in patients with type 1 diabetes and less common in those with type 2 diabetes, due to therapies that less frequently induce hypoglycemia. In the United States, hypoglycemic events contribute to 100,000 emergency department visits annually, costing $120 million [2].
Pathophysiology
Glucose is the main source of energy, and its lack causes the release of glucagon, catecholamines, and growth hormone, leading to adrenergic symptoms. Hypoglycemia can be iatrogenic or secondary to an underlying disease process. Common causes of hypoglycemia in diabetic patients include medication (increased medication intake or decreased oral intake), infection, and worsening kidney function. In non-diabetic patients, common causes include infection, liver disease, and malignancy. Other causes in both groups of patients include Addison disease, adrenal crisis, cardiogenic shock, hypopituitarism (panhypopituitarism), inadequate intake of food, insulinoma, poisoning, stress, and suicide attempts involving anti-diabetic agents [1,3].
Medical History
Taking a thorough history in a hypoglycemic patient is critical for determining the etiology and guiding appropriate management. Below are key elements to address during history-taking:
1. Dietary History
Ask the patient about the timing, content, and size of their last meal. Skipping meals or consuming inadequate carbohydrates can precipitate hypoglycemia, particularly in individuals on glucose-lowering therapies. Recent fasting, changes in eating patterns, or prolonged periods without food (e.g., due to illness or dietary restrictions) should also be noted.
2. Physical Activity
Inquire about recent exercise or physical exertion. Increased physical activity, particularly without appropriate adjustments in food intake or medication, can lead to hypoglycemia. This is especially relevant for individuals on insulin or insulin secretagogues such as sulfonylureas [3].
3. Alcohol Use
Assess the patient’s alcohol consumption, including the amount and timing. Alcohol impairs gluconeogenesis in the liver and can precipitate hypoglycemia, particularly in individuals who have not eaten or who are on glucose-lowering medications.
4. Medication History
For patients with diabetes, a detailed review of their diabetic medication regimen is essential. Obtain information about the specific drugs used (e.g., insulins—categorized as rapid-, short-, intermediate-, or long-acting—or sulfonylureas), doses, and timing of administration. Missing meals or using incorrect dosages are common contributors to hypoglycemia in this population [4]. Additionally, check for the use of other medications that may potentiate hypoglycemia, such as beta-blockers or quinolone antibiotics.
5. Symptoms of Infection or Ischemia
Infections and ischemic conditions can exacerbate hypoglycemia by increasing metabolic demand or altering medication effects. Ask about recent fever, chills, cough, dysuria, chest pain, or other signs and symptoms that could indicate an underlying infection or ischemic event.
6. Drug Overdose or Intentional Harm
In cases of suspected hypoglycemia secondary to drug overdose, particularly with oral hypoglycemic agents like sulfonylureas, inquire about potential intentional overdoses or suicidal ideation. A suicide risk assessment must be conducted in these situations, as hypoglycemia from overdose can be life-threatening [3,4].
7. Family or Social History
If the patient is unable to provide a history, gather collateral information from family members, caregivers, or emergency medical personnel. This can help identify risk factors, such as undiagnosed diabetes or recent changes in behavior or treatment.
Physical Examination
A thorough physical examination is essential for evaluating a hypoglycemic patient and identifying the severity and potential underlying causes of their condition.
1. Initial Assessment
In any patient presenting with coma, altered behavior, or neurological symptoms, hypoglycemia must be considered and excluded early. Immediate bedside glucose measurement is critical to avoid delays in diagnosis and treatment. Early recognition and intervention can prevent irreversible neurological damage.
2. Signs of Neuroglycopenia
Neuroglycopenic symptoms arise from insufficient glucose supply to the central nervous system (CNS). Carefully assess for:
- Level of Consciousness: Evaluate for confusion, lethargy, or unresponsiveness, which may range from mild cognitive impairment to profound coma. The Glasgow Coma Scale (GCS) can quantify the severity of neurological dysfunction.
- Focal Neurological Signs: Perform a focused neurological examination for signs such as hemiparesis or cranial nerve deficits, which may mimic stroke and complicate diagnosis. The resolution of these signs with glucose administration supports hypoglycemia as the cause.
- Seizure Activity: Look for evidence of tonic-clonic movements or postictal states, as seizures may be caused by severe hypoglycemia.
- Ophthalmological Signs: Check for blurred vision or nystagmus, which may indicate neuroglycopenic involvement.
3. Adrenergic Signs
Adrenergic symptoms are the body’s compensatory response to hypoglycemia, mediated by catecholamine release. Key findings include:
- Vital Signs: Look for tachycardia and tachypnea, which are nonspecific but often accompany adrenergic activation.
- Skin Examination: Diaphoresis (profuse sweating) is a hallmark adrenergic response and can serve as a clinical clue.
- Behavioral Symptoms: Assess for signs of agitation, restlessness, or pronounced anxiety, which may be linked to adrenergic stimulation.
The presence of adrenergic symptoms suggests an intact counter-regulatory response, whereas their absence in severe hypoglycemia may indicate an impaired sympathetic nervous system (e.g., in longstanding diabetes with autonomic neuropathy).
4. Whipple’s Triad
Whipple’s triad is critical for diagnosing hypoglycemia and should be confirmed whenever possible [3,4]:
- Symptoms Consistent with Hypoglycemia: Correlate the findings of neuroglycopenic and adrenergic symptoms.
- Low Blood Glucose Levels: Document with point-of-care testing or laboratory confirmation.
- Resolution of Symptoms with Glucose Administration: Reassess the patient after treatment with glucose (e.g., oral glucose or IV dextrose). The resolution of symptoms reinforces the diagnosis.
5. Signs of Underlying Causes
Examine for evidence of potential precipitating conditions:
- Infection: Check for fever, localized tenderness (e.g., chest, abdomen, or urinary tract), or signs of sepsis, as infections increase metabolic demand and can precipitate hypoglycemia.
- Malnutrition: Assess for signs of cachexia or dehydration, which may indicate fasting or poor nutritional intake.
- Drug Overdose: Look for clues such as medication vials, needle marks, or altered mental status in cases of suspected overdose with insulin or sulfonylureas.
6. Secondary Causes
Inquire about and examine for:
- Adrenal Insufficiency: Hypotension, hyperpigmentation, and unexplained fatigue may point to Addison’s disease or secondary adrenal insufficiency.
- Hypopituitarism: Look for evidence of chronic deficiencies such as hypotension, hypoglycemia, and bradycardia.
7. Systematic Re-Evaluation
The examination should be repeated after glucose administration to assess symptom resolution and identify any residual neurological deficits. Persistent focal findings or altered mental status post-treatment may indicate concurrent pathology, such as stroke or seizure disorder.
Alternative Diagnoses
If neurologic or behavioral symptoms persist after treatment with glucose, evaluate for concurrent causes of altered mental status using the mnemonic “TIPS AEIOU” [5]. A CT brain scan may be warranted.
- A – Alcohol
- E – Endocrine/Electrolyte/Epilepsy
- I – Insulin
- O – Overdose/Opioids/Oxygen
- U – Uremia
- T – Toxicologic/Trauma
- I – Infection
- P – Psychiatric/Poisoning
- S – Stroke/Shock
Acing Diagnostic Testing
A comprehensive diagnostic workup is crucial for identifying and addressing the cause of hypoglycemia while initiating timely treatment.
1. Bedside Tests
Rapid bedside testing is the cornerstone for the initial evaluation of hypoglycemia:
- Blood Glucose Measurement:
Venous or capillary blood glucose should be checked immediately using a glucose oxidase strip. A glucose level <3.0 mmol/L confirms hypoglycemia. However, it is critical to remember that the severity of symptoms, rather than the absolute glucose value, determines clinical significance [3]. - Point-of-Care Testing (POCT):
Concurrent bedside tests such as arterial blood gas (ABG) analysis can provide information about acid-base status and potential coexisting conditions like sepsis or metabolic acidosis.
2. Laboratory Tests
Further laboratory investigations should be guided by the clinical presentation and differential diagnosis:
- Formal Glucose Measurement:
If hypoglycemia is detected on a bedside glucose test, a venous blood sample should be sent to the laboratory for a formal plasma glucose level. Importantly, treatment must not be delayed while awaiting these results. - Serum Insulin and C-Peptide:
These are particularly useful when hypoglycemia secondary to endogenous hyperinsulinism or insulin overdose is suspected.- High Insulin and High C-Peptide: Suggest endogenous insulin production, as seen in insulinomas or sulfonylurea ingestion.
- High Insulin and Low C-Peptide: Consistent with exogenous insulin administration [3].
- Cortisol Levels:
A low cortisol level may indicate adrenal insufficiency as a potential cause of recurrent hypoglycemia. - Glucagon Levels:
Although not routinely assessed, glucagon levels can provide insights into counter-regulatory hormone responses during hypoglycemia. - Infection Markers:
Full blood count, inflammatory markers (e.g., CRP, procalcitonin), and blood cultures should be obtained to investigate underlying sepsis or infection. - Toxicology Screen:
Consider when an overdose of oral hypoglycemic agents or other substances is suspected.
3. Imaging Studies
Imaging is not routinely required for all patients with hypoglycemia but should be considered when specific conditions are suspected:
- Chest X-Ray (CXR):
Indicated if a respiratory infection or pulmonary source of sepsis is suspected. - Electrocardiogram (ECG):
Perform in patients with suspected ischemia or when adrenergic symptoms such as tachycardia or chest pain are present. - Neuroimaging (CT or MRI):
Obtain if the patient has persistent neurological symptoms after glucose correction or if there are signs of head trauma, stroke, or other CNS pathology. - Abdominal Ultrasound or CT Abdomen:
Consider in cases of suspected pancreatic pathology, such as insulinoma or pancreatitis.
Key Considerations
- There is no universally defined blood glucose threshold for hypoglycemia, as symptom onset varies among patients. Individual factors, such as baseline glucose control and underlying comorbidities, influence symptomatology [6].
- Diagnostic tests should be tailored based on the clinical scenario to exclude critical conditions like infection, ischemia, or medication overdose. While advanced studies such as serum insulin and C-peptide are valuable, these are rarely performed in the emergency department and are more relevant in specialized or outpatient settings [3].
Risk Stratification
Factors to consider when risk stratifying patients with hypoglycemia include [3,7]:
Severity of hypoglycemia: Mild hypoglycemia can be managed by the patient with oral glucose or food, while severe hypoglycemia may require intravenous glucose and hospitalization.
Frequency of hypoglycemic episodes: Frequent hypoglycemic episodes can increase the risk of developing hypoglycemia unawareness, which may lead to more severe episodes in the future.
Underlying medical conditions: Patients with diabetes who have comorbidities, such as renal insufficiency or liver disease, may be at increased risk for hypoglycemia.
Age and cognitive function: Elderly patients or those with cognitive impairment may be at higher risk for hypoglycemia due to difficulty recognizing symptoms and managing their blood glucose levels.
Lifestyle factors: Patients with poor nutrition or irregular eating patterns may be at increased risk for hypoglycemia.
Management
Patients with hypoglycemia should be placed in a monitored area. If the patient has decreased consciousness or is unconscious, the airway should be protected, but intubation should be avoided prior to the administration of glucose. The means of reversing hypoglycemia depend on the patient’s mental status, ability to cooperate with oral intake, availability of intravenous access, and medical and medication history.
If the patient is conscious and able to cooperate with oral intake, administration of food or liquid rich in simple carbohydrates (e.g., a sugary drink, sugar, candies, or glucose tablets) is preferred. After this, the patient should receive a meal rich in complex carbohydrates, fat, and protein, such as a sandwich.
If the patient is unconscious or unable to cooperate with oral intake and intravenous access is available, administer 50 mL of IV dextrose 50% or 250 mL of 10% dextrose (equivalent to 25 g of dextrose) over a few minutes. A second dose can be administered if the patient’s mental status does not improve.
If intravenous access is not available, 1 mg of IM/SC glucagon can be administered. Glucagon takes longer to normalize mental status (approximately 7–10 minutes), and its effect tends to be short-lived. As glucagon raises blood glucose by mobilizing hepatic glycogen reserves, it is not effective in patients with depleted glycogen stores (e.g., liver failure or chronic alcoholism). Glucagon can also cause vomiting, which may be dangerous if the patient has an altered mental status and cannot protect their airway.
For patients with sulfonylurea overdose, commence therapy with IV dextrose until the patient can tolerate oral intake. If episodes of hypoglycemia recur despite glucose therapy, consider adding SC octreotide 50–100 micrograms. Note that octreotide should only be used for recurrent sulfonylurea-induced hypoglycemic episodes that persist despite glucose therapy [3,5].
Special Patient Groups
Pediatrics
Children are particularly vulnerable to the effects of hypoglycemia due to their higher metabolic rate and limited glycogen stores. Key points in management include:
- Treatment Protocol:
Administer 10% glucose at 5 mL/kg or 25% dextrose at 2.5 mL/kg intravenously for acute hypoglycemia. Avoid the use of 50% dextrose in this population, as its hypertonicity increases the risk of thrombophlebitis and local tissue injury [8]. - Medication for Refractory Cases:
For persistent hypoglycemia caused by hyperinsulinemia (e.g., from congenital hyperinsulinism or sulfonylurea overdose), octreotide is effective at a dosage of 1 μg/kg subcutaneously (maximum 50 μg). This medication inhibits insulin secretion and provides a targeted intervention [8]. - Long-Term Considerations:
Recurrent hypoglycemia in children warrants further investigation into metabolic or endocrine disorders, including inborn errors of metabolism, adrenal insufficiency, or insulinoma.
Pregnant Patients
Pregnant patients with diabetes, particularly those on insulin therapy, face a higher risk of hypoglycemia due to physiological changes during pregnancy, including increased insulin sensitivity in the first trimester.
- Incidence:
Up to 50% of pregnant patients with diabetes experience at least one episode of severe hypoglycemia during pregnancy, especially in the first trimester [4]. - Management and Prevention:
- Careful Insulin Titration: Frequent monitoring and adjustment of insulin doses are essential to balance optimal glycemic control with the prevention of hypoglycemia.
- Dietary Counseling: Pregnant patients should be educated on consuming regular, balanced meals with adequate carbohydrate intake to prevent fasting hypoglycemia.
- Monitoring: Emphasize regular blood glucose monitoring, as symptoms may be subtle or atypical.
- Fetal Considerations: Prompt correction of maternal hypoglycemia is critical to prevent adverse effects on the fetus, including hypoxic injury from prolonged episodes.
Geriatrics
Older adults often experience atypical presentations of hypoglycemia, and their management is complicated by comorbidities, polypharmacy, and age-related physiological changes.
- Atypical Presentations:
Hypoglycemia in geriatric patients may lack typical adrenergic symptoms like tremors or sweating. Instead, symptoms such as confusion, lethargy, or falls may predominate, potentially delaying diagnosis. - Risk Factors:
- Polypharmacy: Concurrent use of insulin, sulfonylureas, or other glucose-lowering agents increases hypoglycemia risk.
- Renal Impairment: Reduced clearance of medications such as sulfonylureas or insulin exacerbates the risk of prolonged hypoglycemia.
- Nutritional Deficits: Poor oral intake or prolonged fasting may contribute to hypoglycemia.
Intubated Patients
For intubated or sedated patients, hypoglycemia can be difficult to recognize because mental status changes are masked. In these cases, frequent glucose monitoring is essential [5].
When To Admit This Patient
Admission Criteria
Patients with hypoglycemia generally require admission to an observation unit or the general ward for evaluation and treatment of the underlying cause, as well as titration of diabetic medication.
Patients with unexplained or recurrent hypoglycemia should be admitted to a monitored area. Individuals taking sulfonylureas have an increased likelihood of experiencing recurrent and delayed-onset episodes of hypoglycemia. Consultation with a toxicologist and psychiatrist should be considered for patients who overdose on their diabetic medication [3,7].
Discharge Criteria
The patient should only be discharged if the cause of hypoglycemia is identified and deemed benign, they have fully recovered, are tolerating oral intake well, and have had no recurrence of hypoglycemic episodes after a 4-hour period of observation. Discharge advice should include guidance on nutrition and recognition of hypoglycemia symptoms. Patients should be advised to ingest glucose in case of symptoms [3].
Referral
If discharged from the ED, patients should be referred to their primary physician or specialist for follow-up. Patients should also be advised to always carry sugar or candy to ingest in case hypoglycemic symptoms arise [3].
Revisiting Your Patient
You examine your patient in the examination room. Upon examination, you notice a decreased level of consciousness, but otherwise, the exam is unremarkable. During the examination, the nurse obtains IV access and administers a bolus dose of intravenous glucose. Much to the relatives’ relief and amazement, the patient returned to her normal behavior within 5 minutes. The patient herself reported lower urinary tract symptoms with a low-grade fever over the last two days. The relatives also reported administering her insulin according to her daily regimen, without being cautious about her reduced food intake.
In addition, blood investigations revealed that her renal function had significantly deteriorated since her last primary care visit, despite continuing on the same insulin regimen. The patient was subsequently admitted to a general ward for further evaluation and management.
Recommended Free Open Access Medical Education (FOAM) resources
Jameson B. Oh, sugar! Paediatric hypoglycaemia. St. Emlyn’s Blog. https://www.stemlynsblog.org/paediatric-hypoglycaemia/. Published January 2012. Accessed December 25, 2024.
Hypoglycemia. WikEM. https://wikem.org/wiki/Hypoglycemia. Accessed December 25, 2024.
Author
Rok Petrovčič
Attending Physician - UKC Maribor / University Medical Centre Maribor
Listen to the chapter
References
Mathew P, Thoppil D. Hypoglycemia. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2022. Updated July 23, 2022. Accessed February 24, 2023. https://www.ncbi.nlm.nih.gov/books/NBK534841/
Maheswaran AB, Gimbar RP, Eisenberg Y, Lin J. Hypoglycemic events in the emergency department. Endocr Pract. 2022;28(4):372-377.
Ravert D. Hypoglycemia. In: Mattu A, Swadron S, eds. CorePendium. Burbank, CA: CorePendium, LLC; 2021. Updated August 25, 2021. Accessed February 24, 2023. https://www.emrap.org/corependium/chapter/rec3z0v69Pks65AZg/Hypoglycemia#references
Jalili M. Type 2 diabetes mellitus. In: Tintinalli JE, ed. Tintinalli’s Emergency Medicine. 7th ed. New York, NY: McGraw Hill; 2011:1431-1432.
Nickson C. Hypoglycemia. In: Life in the Fast Lane. Accessed February 24, 2023. https://litfl.com/hypoglycemia/
Frier BM. Defining hypoglycemia: what level has clinical relevance? Diabetologia. 2009;52(1):31-34.
Oyer DS. The science of hypoglycemia in patients with diabetes. Curr Diabetes Rev. 2013;9(3):195-208.
May N. Oh, sugar! Paediatric hypoglycaemia. In: St. Emlyn’s Blog. Accessed March 1, 2023. http://stemlynsblog.org/paediatric-hypoglycaemia/
Reviewed and Edited By
Arif Alper Cevik, MD, FEMAT, FIFEM
Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.
