CONTENTS
- Rapid Reference 🚀
- Why hypoglycemia is dangerous
- Symptoms
- Diagnosis
- Causes
- Investigation
- Treatment
- Prevention of hypoglycemia in the ICU patient
- Persistent hypoglycemic encephalopathy
- Podcast
- Questions & discussion
- Pitfalls
- Prolonged severe hypoglycemia can cause permanent brain damage, similar to anoxic brain injury.
- Hypoglycemia is most dangerous among intubated and sedated patients, because mental status changes won't be immediately evident.
- Overall, hypoglycemia is far more dangerous than hyperglycemia. When dosing insulin in an acute care setting, it's always safer to leave the patient in a mildly hyperglycemic range.
autonomic symptoms (sympathetic activation)
- Diaphoresis.
- Tremulousness, anxiety.
- Tachycardia, palpitations, increased blood pressure.
- Hunger.
brain dysfunction is usually the most obvious clinical finding
- Confusion.
- Visual changes (blurred vision, diplopia).
- Slurred speech, dizziness.
- Seizures.
- Eventually: lethargy, stupor, coma.
defining hypoglycemia
- Definitions vary. Overall, there are two main considerations:
- How low is the glucose?
- Moderate hypoglycemia: 40-70 mg/d (2.2-3.9 mM). (26696689)
- Severe hypoglycemia: <40 mg/dL (<2.2 mM). Levels <40-50 mg/dL may cause coma.(Vincent 2023)
- Is the patient symptomatic?
- Absence of symptoms is certainly reassuring.
- Unfortunately, ICU patients who are intubated/sedated may be impossible to evaluate.
point-of-care glucose level
- This is the front-line test due to speed.
- Can be artificially elevated by maltose (in patients receiving IVIG or peritoneal dialysate).
- Source of blood?
- Fingerstick glucose may be inaccurate in patients with poor perfusion.
- It may be ideal to obtain blood from an arterial or venous catheter, to avoid perfusion problems.
- If fingerstick glucose is low, but you doubt whether it is an accurate measurement:
- 1) Send blood to lab for glucose level.
- 2) If patient is symptomatic or sedated, give IV dextrose immediately (without waiting for confirmatory lab results).
laboratory measurement of glucose
- This is the gold-standard (e.g., it may be used to double-check fingerstick results in questionable cases).
- As noted above, treatment should not be delayed while awaiting a confirmatory laboratory result, unless the patient is awake and mentating normally without symptoms.
- Laboratory glucose measurement can be low if blood sits around for a long time before processing, or if there is severe leukocytosis.
medications
- Insulin:
- Accidental, suicidal, iatrogenic, factitious.
- Drugs that increase insulin secretion:
- Sulfonylureas (glimepiride, glipizide, especially glyburide).
- Meglitinides (repaglinide, nateglinide).
- Pentamidine.
- Other mechanisms (evidence for many of these drugs is questionable)
- Diabetes medications not listed above (e.g., SGLT-2 inhibitors, metformin). These usually don't cause hypoglycemia on their own, but may synergize with other risk factors.
- Antibiotics (fluoroquinolones, sulfonamides, pentamidine, artemisinin antimalarials).
- Neurologic: Phenytoin, selegiline, valproate.
- Psychiatric: doxepin, haloperidol, fluoxetine, lithium.
- Cardiovascular: Nonselective beta-blockers (propranolol, nadolol), ACE inhibitors.
- Other:
- NSAIDs (especially indomethacin).
- Quinine.
- Hydroxychloroquine.
- Salicylate intoxication.
specific diseases
- Adrenal insufficiency.
- Myxedema coma.
- Hepatic failure.
- Sepsis.
- Renal failure (usually not by itself; note that renal dysfunction may cause accumulation of many medications).
- Insulinoma or various malignancies (e.g., mesenchymal tumors, hematologic malignancies).
- Status post gastric bypass surgery.
intake/use mismatch
- Starvation, anorexia nervosa.
- Exercise.
- Pregnancy/lactation.
- Alcohol binging.
history is key
- Medication history:
- The most common culprit is insulin or sulfonylurea misuse.
- Review new medications or dose changes (potentially causative medications are listed in the section above.).
- Changes in renal or hepatic function may cause drug accumulation.
- Adequacy of oral intake? Recent alcohol binge?
- Evaluate for features that may suggest sepsis, chronic adrenal insufficiency, or hepatic failure.
if cause remains unclear, obtain labs:
- Insulin level:
- Insulin level >3 microunits/ml (21 pM) in context of hypoglycemia suggests pathologically excessive insulin levels. This may reflect either endogenous insulin synthesis or exogenous insulin administration.
- Unfortunately, some synthetic forms of insulin may not be detected by the assay (e.g., glargine).
- C-peptide level:
- Measures only endogenous insulin production, allowing differentiation between endogenous over-production of insulin versus exogenous insulin administration.
- C-peptide level >0.2 nM (0.6 ng/ml) in the context of hypoglycemia suggests pathologically elevated insulin secretion by the pancreas.
- Beta-hydroxybutyrate:
- Elevated levels (above ~2.7 mM) argue against a hyperinsulinemic state (because insulin suppresses ketone production). Thus, elevated levels would suggest entities such as starvation, alcoholic ketoacidosis, or sepsis.
- Cortisol level to exclude adrenal insufficiency:
- Generally a stressed, hypoglycemic patient should have somewhat elevated levels of cortisol. Low levels should alert to the possibility of adrenal insufficiency.
- When in doubt, an ACTH stimulation test should be performed to clarify.📖
- TSH (thyroid stimulating hormone).
- Liver function tests.
Below is a general strategy for severe hypoglycemia with threatened brain injury. Glucose should be monitored carefully throughout (at least q1hr, or more frequently). Treatments should be titrated to achieve a safe glucose level (e.g., 100-200 mg/dL or 5.6-11.2 mM). Pushing the glucose too high can be counterproductive, as this can stimulate endogenous insulin release leading to rebound hypoglycemia. Continue working through the algorithm until the patient's glucose is stabilized.
step #1: IV dextrose bolus
- The traditional treatment has been 50-100 ml of D50W (1-2 ampules of D50W).
- This is readily available and easy to administer.
- D10W is another option (~100-200 ml usually; may be pushed in several 50-ml boluses). 🌊
- Advantages: D10W is less irritating to the veins than D50W. D10W may have a lower risk of overshoot hyperglycemia.(15983093)
- Disadvantage: D10W takes slightly longer to give, so it may be less useful for patients with profound symptoms who need immediate treatment (e.g., seizure, coma).
- If the patient doesn't have IV access, then place an IV or intraosseous line immediately.
step #2: food (if possible)
- If the patient wakes up and is able to tolerate oral nutrition, this is the most efficient way to provide carbohydrate.
- For example:
- A Snickers bar contains 215 Calories. This is the same number of calories as 1.25 liters of D5W.
- A pint of Ben & Jerry's ice cream contains ~1,100 calories. That's equal to 6.5 liters of D5W!
- Calorically dense foods with a high carbohydrate content are best. Ice cream or chocolate are good choices.
- For intubated patients with enteral access, tube feedings should be given.
step #3: dextrose infusion
- Either D5W or D10W are safe for peripheral infusion.
- The infusion rate depends on severity of hypoglycemia. A typical rate might be ~150 ml/hr D5W, or 75 ml/hr D10W.(24286945) Titrate to effect, based on frequent glucose measurement.
- If the patient already has central access, you can give D20W or D50W centrally. However, placement of a central line for the sole purpose of treating hypoglycemia is generally unnecessary.
step #4a: octreotide 💊
- Octreotide may be utilized in patients with sulfonylurea intoxication.
- Dose: Load with 100 mcg IV once, then continue a maintenance dose of 50 mcg subcutaneously q6hr.
- Rebound hypoglycemia can occur within 24 hours of stopping the octreotide, so patients should be monitored during this period.
step #4b: steroid
- This is not a standard therapy for hypoglycemia, but it may be useful for selected patients who aren't responding favorably to the usual interventions. 🌊
- Steroid induces a state of insulin-resistance. Steroid is especially effective in the following situations:
- (1) In adrenal insufficiency, steroid administration is essential.📖
- (2) Massive insulin overdose may cause patients to require enormous doses of dextrose (which may lead to problems regarding hypokalemia and volume overload). Steroid administration counteracts the insulin overdose. The goal of steroid administration isn't to avoid giving dextrose entirely, but rather merely to reduce the dextrose requirement to a manageable level. This may avoid volume overload, electrolyte abnormalities, and the requirement for a central line.(Tariq et al. 2018)
- Any steroid will work, but IV hydrocortisone is preferred due to its rapid onset and relatively short duration of action (8-12 hours), which allows for titration.
- Start with 100 mg IV hydrocortisone Q6hr.
- Titrate based on glucose level.
- If hypoglycemia is mild and the patient is able to take PO intake, provide oral carbohydrate (e.g., juice).
- For intubated patients with enteral access, this may be provided via orogastric tube.
- Avoid peripheral D50W if you don't need it, because over time repeated doses can cause sclerosis of peripheral veins.
- To prevent recurrence, consider providing additional food that contains complex carbohydrates.
The traditional approach to severe hypoglycemia in a patient without IV access is to give 1 mg of glucagon intramuscularly. However, this is not a terrific idea for several reasons:
- Glucagon may not work, if the patient’s liver glycogen stores are depleted.
- Glucagon can stimulate vomiting, which may be particularly dangerous if the patient has altered mental status and cannot protect their airway.
- Even if the glucagon doesn’t cause vomiting, it may cause nausea that impairs the ability to feed the patient later on.
- Glucagon takes 10-15 minutes to work, which seems like a fairly long delay for a patient with severe hypoglycemia.
Thus, the approach to severe hypoglycemia in a critically ill patient is to obtain IV access immediately (e.g., with an intraosseous line or intravenous line).
- Upon admission to the ICU discontinue any oral hypoglycemic medications. Hyperglycemia should be controlled with insulin therapy only.
- Be conservative with insulin dosing:
- Don't try to achieve tight glycemic control. A glucose target of <220 mg/dL (<11.1 mM) is fine for most patients. Patients with diabetes and elevated hemoglobin A1C >7 may do better if their glucose is allowed to drift higher (up to ~250 mg/dL)(13.9 mM).📖
- When in doubt, dose insulin conservatively. Hyperglycemia is less dangerous than hypoglycemia.
- Consider reducing the insulin dose if the patient becomes NPO, or if steroid doses are decreased.
- Insulin dosing can be tricky. Among all medications, insulin is one of the most prone to serious dosing errors.
- Patients with cirrhosis or acute hepatic failure tend to develop hypoglycemia, so monitor their glucose levels and avoid giving them insulin. Some patients with severe hepatic failure will require a continuous dextrose infusion to avoid hypoglycemia.
A sustained episode of hypoglycemia may cause brain injury which is persistent or even permanent. This injury has many similarities to hypoxic-ischemic brain injury.
neuroimaging features
- (1) The most common finding is T2/FLAIR hyperintensity with strongly restricted diffusion affecting gyri in the parieto-occipital and temporal regions.(31589567)
- (2) Basal ganglia can be involved, which may be a poor prognostic sign.(31589567)
- (3) Characteristically there is sparing of the thalami, white matter, and cerebellum. This may help differentiate hypoglycemic injury from hypoxic-ischemic injury (which usually involves the thalami and cerebellum).(31589567)
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To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Symptomatic hypoglycemia is an emergency, with a risk of causing permanent brain damage. When in doubt, it's always better to err on the side of providing immediate treatment (if you're wrong and the patient gets slightly hyperglycemic, that's OK).
- Patients with any sort of neurologic alteration (e.g., confusion, seizure, coma) should always have a STAT fingerstick glucose to exclude hypoglycemia.
- After you treat hypoglycemia, follow the patient's glucose carefully. Hypoglycemia frequently recurs. For example, insulin or sulfonylurea overdoses will out-last the glucose you give to the patient.
- The cause is usually a medication. Before you start hunting for an insulinoma, double-check the medication list.
Guide to emoji hyperlinks
- = Link to online calculator.
- = Link to Medscape monograph about a drug.
- = Link to IBCC section about a drug.
- = Link to IBCC section covering that topic.
- = Link to FOAMed site with related information.
- = Link to supplemental media.
References
- 15983093 Moore C, Woollard M. Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial. Emerg Med J. 2005 Jul;22(7):512-5. doi: 10.1136/emj.2004.020693 [PubMed]
- 24286945 Alsahli M, Gerich JE. Hypoglycemia. Endocrinol Metab Clin North Am. 2013 Dec;42(4):657-76. doi: 10.1016/j.ecl.2013.07.002 [PubMed]
- 26696689 American Diabetes Association. 13. Diabetes Care in the Hospital. Diabetes Care. 2016 Jan;39 Suppl 1:S99-104. doi: 10.2337/dc16-S016 [PubMed]
- 27099902 Bansal N, Weinstock RS. Non-Diabetic Hypoglycemia. 2020 May 20. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000– [PubMed]
- 31589567 de Oliveira AM, Paulino MV, Vieira APF, McKinney AM, da Rocha AJ, Dos Santos GT, Leite CDC, Godoy LFS, Lucato LT. Imaging Patterns of Toxic and Metabolic Brain Disorders. Radiographics. 2019 Oct;39(6):1672-1695. doi: 10.1148/rg.2019190016 [PubMed]
PMID: 36464132 DOI: 10.1016/j.eprac.2022.11.010