Hypoglycemia

Kenny Banh, MD & Jose Acosta, University of California

Edited By: Steven Davis MD, George Washington University

FOAMed Contributor: Ryan McLaughlin, MD, Virginia Commonwealth University 

Last Updated: November, 2019

Case Study

A 68-year-old female who is a known diabetic on insulin detemir (Levemir) at home is brought in by EMS for a hypoglycemic event. The spouse found the patient unconscious at home. Point of care glucose was 42 mg/dL initially. 1 amp (50mg) of  IV dextrose was given. Pt had a resolution of her altered mental state. Patient is uncertain what happened but thinks that she might have switched her short acting insuling with her long acting. Repeat glucose is now 131 mg/dL. BP 140/94, HR 84, RR 16 SpO2 is 96% on room air. She has no focal neurologic deficits on exam and has no other pertinent exam findings. The patient’s husband asks “Can we go home now?”  

Objectives

The objectives of this module will be to:

1. Review the signs and symptoms associated with hypoglycemia.
2. Review the methods of treating a patient with hypoglycemia.
3. Review the disposition of a patient presenting to the emergency department with hypoglycemia.

Introduction

Hypoglycemia accounts for approximately 7% of emergency department visits for altered mental status within the US. In diabetic patients, approximately 25% will experience repeated episodes of hypoglycemia.

Hypoglycemia is clinical syndrome of altered autonomic function and impaired cognition that can occur as serum glucose levels fall below normal physiologic thresholds.  The serum glucose level at which symptoms of hypoglycemia occur vary among patients, and may also vary between hypoglycemic events in a given patient; however, serum glucose levels < 70 mg/dL are generally considered consistent with hypoglycemia.

Initial Actions and Primary Survey

The initial approach to the patient with hypoglycemia begins with the primary survey to reduce the likelihood of death or permanent disability within the minutes-to-hours following initial presentation.  Altered cardiovascular function (e.g. tachycardia, hypertension) and neurologic disability (e.g. diminished Glascow Coma Scale (GCS) score, focal neurologic deficit) may suggest autonomic and cognitive dysfunction, respectively.  The primary survey may further reveal signs of decompensated underlying disease (e.g. shock state) or classic toxidromes (e.g. ethanol intoxication) that suggest a precipitating cause for acute hypoglycemia.

Following completion of the primary survey and associated interventions, immediate diagnostic evaluation should include point-of-care glucose testing and EKG acquisition.  Additional testing is determined according to results of a thorough history and examination in search of precipitating causes for acute hypoglycemia, and may include serum electrolytes, liver-associated enzymes, toxicologic screening, endocrinologic evaluation and a search for underlying infection.

While signs and symptoms of hypoglycemia generally promptly resolve following administration of glucose, additional testing may be indicated when diagnostic uncertainty remains, and may include cardiac biomarkers (troponin), neuroimaging (CT brain), EEG testing and psychiatric evaluation.

Presentation

Signs and symptoms of hypoglycemia are broadly divided into those resulting from altered (typical increased) autonomic function, and those associated with diminished cognitive function.  Signs and symptoms associated with increased adrenergic tone may include palpitations, tremor, anxiety, tachycardia and hypertension. Increased cholinergic tone in hypoglycemia may result in increased hunger, diaphoresis and paresthesias.  Diminished cognitive function in hypoglycemia results from neuroglycopenia, and may present as headache, dizziness, weakness, visual disturbances, focal neurologic deficits, and varying levels of altered consciousness from confusion to seizure and coma.  

Signs of cognitive dysfunction classically predominate in most cases of hypoglycemia, but rapid decreases in serum glucose levels will also produce signs of altered autonomic function to some degree.  Signs and symptoms resulting from hypoglycemia tend to persist until serum glucose levels are corrected. Persistent symptoms and signs may aid in differentiating hypoglycemia from other conditions with similar presentations.

In patients with poorly controlled diabetes and elevated baseline glucose levels (as determined by hemoglobin A1C levels or by history), symptomatic hypoglycemia may occur at serum glucose levels significantly above 70 mg/dL.  Conversely, patients with recent or frequent prior episodes of hypoglycemia (e.g. supratherapeutic insulin administration, or fasting state), or those taking medications that may mask autonomic symptoms of hypoglycemia (e.g. beta-adrenergic blockers), may not display signs or symptoms with subsequent hypoglycemia despite serum glucose levels significantly below 70 mg/dL.  The clinician must therefore maintain a high level of suspicion for hypoglycemia in all patients with poorly controlled diabetes and classic symptoms regardless of serum glucose level, as well as asymptomatic patients with poorly controlled diabetes who may nonetheless have severely depressed serum glucose levels.

Hypoglycemia more frequently occurs in patients with known diabetes following administration of supratherapeutic doses of antihyperglycemic therapies (either accidental or intentional).  Insulin and insulin secretagogues (sulfonylureas and meglitinides) are most commonly implicated. In both diabetic and nondiabetic patients, hypoglycemia can result from conditions that impair glycogenolysis and gluconeogenesis (e.g. advanced liver disease, alcohol intoxication), increase glucose consumption (e.g. critical illness), decrease glucose availability (e.g. fasting state), or increase insulin production (e.g. insulin-secreting tumor).  A significant number of medications are also associated with hypoglycemia in both diabetic and nondiabetic patients. 

Table 1: Potential Underlying Causes in Hypoglycemia

The differential diagnosis of hypoglycemia is broad and includes conditions that acutely alter autonomic function and those that diminish cognition. See Table 2 for the differential of hypoglycemia.

Table 2: Hypoglycemia – Differential Diagnosis

Diagnostic Testing

Point-of-care (POC) glucose testing is readily available in most clinical settings, and offers an immediate diagnosis in most patients with suspected hypoglycemia.  POC glucose testing should be performed in all patients with suspected hypoglycemia or at risk for hypoglycemia, and should promptly follow completion of the primary survey.  While generally reliable, POC glucose testing may provide inaccurate results in certain scenarios, including extremely elevated and extremely decreased serum glucose levels, and significantly delayed testing of obtained blood samples.  In these scenarios, testing should be repeated, ideally from venipuncture specimens and with formal laboratory assays (e.g. basic metabolic panel [BMP] testing).

Additional testing should target potential precipitating causes for confirmed hypoglycemia, as well as conditions that may mimic symptoms of hypoglycemia in cases of diagnostic uncertainty.

When hypoglycemia is suspected to result from acute infection, reasonable additional testing may include:

• CBC with differential
• Urinalysis
• CXR
• Urine Gram Stain & Culture
• Blood Gram Stain & Culture
• Viral PCR testing
• CSF Analysis

In patients with underlying hepatic or endocrinologic dysfunction, additional testing may include:

• Liver-Associated Enzymes
• Thyroid Function Tests
• Serum Cortisol

In otherwise healthy nondiabetic patients, in addition to the above-mentioned tests, also consider:

• Proinsulin
• C-peptide
• B-hydroxybutyrate
• Serum Ethanol
• Toxicology Screens
  

Treatment

Any patient presenting with signs and symptoms consistent with hypoglycemia and a blood glucose level < 70 mg/dL should receive treatment with supplemental glucose (dextrose). Route of glucose administration should be determined according to patient’s acuity and associated symptoms.  Given the exceedingly low likelihood of adverse events, glucose administration should not be delayed while awaiting diagnostic confirmation in patients with presentations suggestive of hypoglycemia..

Oral: Oral glucose is the preferred route of administration when it can be given safely in awake and alert patients without contraindication to oral medications. In adults, a total of 300g (1200cal) of carbohydrate should be given (soda, juice, sandwich, snacks).  Supplementation with complex carbohydrates will allow for sustained normoglycemic levels.

Intravenous Glucose: Intravenous bolus administration of 100ml of 10% Dextrose in Water (D10) is recommended in patients not otherwise suitable for oral glucose administration.  Alternative dosing involves 50 ml of 50% Dextrose in Water (D50). D50 pre-mixed ampules are readily available in many clinical environments (and all emergency departments), and consequently represent a first-line intervention for hypoglycemia for many clinicians.  However, D50 may be associated with a greater risk of rebound hypoglycemia, hypertonic toxicity, and post-treatment hyperglycemia.

Monitor mental status and blood glucose measurements every 15-30 min after glucose administration for 1-2 hours, and then as needed for persistent hypoglycemia thereafter. Persistent hypoglycemia may require additional glucose boluses or continuous infusions of glucose. Consider giving parenteral thiamine at the time of glucose administration in patients at risk for thiamine deficiency  to prevent Wernickes encephalopathy (e.g. starved state, chronic alcohol consumption). 

Glucagon: Intramuscular glucagon may be used when there is no IV access and oral glucose cannot be safely given. In adults, administer 1 mg IM.  In pediatric patients < 20 kg, administer 0.5 mg IM. In conditions with depleted glycogen stores (elderly, advanced liver disease, starved state), glucagon may not be effective.

Octreotide: Intravenous octreotide may be useful in the setting of persistent hypoglycemia not responsive to other therapies (e.g. sulfonylurea toxicity). Initial dose of octreotide is 50-75 mcg SQ Q6hrs or 50-125 mcg/hr IV continuous infusion. Glucose should be checked every 1-2 hours after starting octreotide.

Disposition

Typically these patients will require several hours of close monitoring. Additional episodes of hypoglycemia need to be aggressively treated and only after ability to maintain normoglycemia should discharge be considered.

Discharge criteria for patients following a symptomatic episode of hypoglycemia:

• Episode is brief.
• Full neurologic recovery occurs.
• Patient is able to eat.
• No major comorbid conditions that require hospital admission exist.
• Cause of the hypoglycemic episode is identified and addressed.
• Treatment plan to prevent future episodes is understood by the patient.
• Hypoglycemia is accidental.
• Relapse is unlikely (no long-acting insulin or oral agents, nor prolonged excretion or metabolism).
• Patient displays ability to perform home glucose monitoring.
• Responsible person is able to be with the patient.
• Follow-up is arranged.

Admission is often appropriate if any of the above-listed conditions are unmet.

Pearls and Pitfalls

• Always consider hypoglycemia when evaluating a patient presenting with altered mental status or hyperautonomic symptoms.
• Beta-blockers can mask adrenergic signs of hypoglycemia.
• Administer glucose based on clinical presentation if a bedside glucometer is unavailable and laboratory confirmation will delay treatment.
• Feed patients following a response to IV glucose if they are able to eat.
• Administer IM glucagon in symptomatic hypoglycemic patients who are unable to take oral glucose and in IV access is not available.
• Strongly consider admitting patients who are on long-acting insulin or oral insulin secretagogues (sulfonylureas, meglitinides).
  

Case Study Resolution

The patient was found to have a glucose of 65 mg/dL on her basic metabolic panel. Despite oral refeeding and continued monitor for several hours, the patient continues to have episodes of moderate hypoglycemia. The patient was admitted for observation due to her age and  need for 6-8 hour observation to ensure sustained serum normoglycemia for the duration of action of her Levemir insulin.. Upon admission, the patient stated that she lost her reading glasses earlier that evening. She was subsequently discharged the following day and scheduled an appointment with her optometrist the day of her discharge.

Levemir has an onset of action of 1-2 hours, has a peak action around 6-8 hours, and lasts 24 hours. 

FOAMed Resources

• EMCrit: Hypoglycemia Chapter from the “Internet Book of Critical Care”

https://emcrit.org/ibcc/hypoglycemia/

• EMCrit: Case Reports on Insulin Overdose

https://emcrit.org/pulmcrit/insulin-poisoning/

• Life in the Fast Lane: Critical Care Compendium on Hypoglycemia

https://litfl.com/hypoglycemia/

• Life in the Fast Lane: Case Report on Hypoglycemia

https://litfl.com/hypoglycemia-but-how/

• Life in the Fast Lane Tox Library: Article on Poisons Inducing Hypoglycemia

https://lifeinthefastlane.com/tox-library/antidote/glucose/

• CoreEM: Pharmacology of Insulins

https://coreem.net/core/pharmacology-of-insulins/

• Taming the Sru: Hypoglycemia in the Setting of Neonatal Shock: 

http://www.tamingthesru.com/blog/grand-rounds/recap-08012018

References

Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, Service FJ. Evaluation and management of adult hypoglycemic disorders: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2009;94:709–728

Orman, Rob, and George Willis. “Hypoglycemia.” EMRAP, June 2017, www.emrap.org/episode/dontfearthe/hypoglycemia.

Kiefer M, Gene H, Alter H, Barger J. Dextrose 10% in the treatment of out-of-hospital hypoglycemia. Prehosp Disaster Med. 2014;29(2):190-194

Moore C, Woollard M. Dextrose 10% or 50% in the treatment of hypoglycemia out of hospital? A randomized controlled trial. Emerg Med J. 2005;22(7):512-515.

Smeeks FC. Hypoglycemia. Available on emedicine at; http://emedicine.medscape.com/article/767359-overview. Accessed June 16, 2010.