Hypoglycaemia

Definitions

• Definition of hypoglycaemia is a blood glucose of < 4
  • • Level 1 hypoglycaemia = 3-3.9
    • Level 2 hypoglycaemia = <3
    • Level 3 hypoglycaemia = cognitive impairment requiring external assistance, no CBG value attached
• Symptoms can also be used to define severity of hypoglycaemia
  • • Mild – conscious, orientated, able to swallow
    • Moderate – confused but able to swallow
    • Severe – unconscious or nil-by-mouth, or fitting or very aggressive. Also classed as severe if required assistance, and non-severe if self-managed
• Looming hypoglycaemia (CBGs 4-6)
  • • Requires more careful monitoring and perhaps modification of treatment/oral intake, especially if inpatient.
    • Some patients with poor glycaemic control can experience symptoms when CBG >4, but no confusion. Treat these with a snack (banana, meal, bread)
    • Target CBG range for most inpatients should be 6-10. Consider prescribing PRN IV dextrose for patients on insulin
• Hypoglycaemia in non-diabetics
  • • CBG < 4 can be normal in non-diabetics (if hungry, exercising etc).
    • Level 1 is of no real significance in non-diabetics.
    • About 1/3 of people without DM can get to level 2.
    • However pathological hypoglycaemia in a non-diabetic is defined as <2.2 (eg in insulinoma)

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Symptoms, the hypo-cascade and risk

• In normal people
  • • If CBG <5 insulin starts to fall (due to beta bells detecting low blood sugar)
    • Glucagon starts to rise (the latter in response to the insulin fall, not the CBG fall)
    • This is enough to stabilise blood sugar
• In diabetics on insulin
  • • When blood sugar falls due to exogenous insulin, there is no glucagon release.
    • At around CBG of 3.5 adrenaline starts to rise (at lower CBGs if impaired awareness) – shaking, sweating etc (although if people frequently run high sugars they can get symptoms at 5 or 6).
    • Cognitive dysfunction tends to occur around 3
    • Below this you can get ECG changes, seizures, loss of consciousness
• Risks
  • • The annual prevalence of severe hypoglycaemia is 35% in T1DM
    • If a patient develops severe hypoglycaemia in the community – they have a 12 month mortality of >20%
    • Severe hypoglycaemia only rarely kills you at the time – but the increased mortality is due to higher risks of inflammation, thrombosis, cancer, other events in the coming weeks/months
• Clinical features
  • • Tremor, palpitations, sweating, hunger, blurred vision
    • Then later: reduced concentration, EEG changes, irritability, confusion, drowsiness, fits. Neurological deficits can be permanent.
    • Nocturnal hypoglycaemia can cause fatigue, headache and a hangover sensation (check CBGs at 2-3am, and snack before bed)
• Hypo unawareness – more common in long standing type 2 diabetics and T1 DM

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Acute treatment of hypoglycaemia

• Stop any IV insulin (and check for any pumps including patch-pumps)
• Mild and moderate hypoglcyaemia (see symptoms above) are treated the same if able to eat/drink
  • • Provide around 15g of quick acting carbohydrate
    • Options are
      • • Glucose tablets
        • 200ml fruit juice – but not in CKD as high K+ content
        • Half a can of fizzy drink
        • 4 heaped teaspoon sugar in water (unless taking acarbose)
    • Chocolate not recommended (due to the fat content)
• In moderate hypoglycaemia, if able to swallow but uncooperative – use 2 tubes of 40% glucose gel (squeeze into mouth)
• Then: recheck CBG in 15 minutes – the 15: 15 rule – 15g carbs, repeat CBG in 15 mins
• Repeat up to 3 times if patient remains hypoglycaemic
• If still hypoglycaemic, or patient too drowsy, treat as severe hypoglycaemia
  • • Give 100ml of 20% glucose or 200ml of 10% glucose
    • If no IV access – 1mg IM glucagon (recheck in 15 minutes and repeat if needed. Glucagon can take 15 mins to work).
    • Glucagon is less effective if patient malnourished, has CLD, intoxicated with ETOH, sulfonuylurea-induced, or has repeated hypoglycaemia
    • If CBG < 4 in 10 mins, repeat treatment
• Then, once CBG > 4
  • • Give around 20g of long acting carbohydrate (2 biscuits, slice of bread, 250ml milk). You can undertreat or overtreat with glucose – consider your patient weight
    • If glucagon given – give 40g long acting carbohydrate instead
    • If a patient is NBM – start 10% glucose at 100ml/hr
    • If NG tube in situ – can give a nutritional supplement like Ensure or Fortijuice
    • Continue frequent CBG monitoring for the next 24-48 hours (If hypoglycaemia was caused by long acting insulin or gliclazide, the risk of hypos will persist for 36 hours, and especially if renal impairment)
    • If the patient was on IV insulin – you can restart once CBG >4 (usually add IV glucose alongside)
    • Do not omit next insulin dose but review and often will adjust doses
    • Do not start sliding scale to stabilise CBGs – any IV insulin increases risk of hypoglycaemia
    • For intentional insulin overdose – see prescribed drug toxicities. This is managed quite differently
• Later, can ask about
  • • Their diabetes treatment (changes, errors in administration etc)
    • How often the patient gets hypoglycaemia
    • How often they check their CBGs (and their target range)
    • Diet, ETOH, exercise, new medications (including recent steroid use)
    • Risks – their hypoglyaemia awareness, injection sites, recent illness, diet, pregnancy, self-harm, occupation (night shift work)
• Out of hospital hypoglycaemia: who to admit
  • • Judge this on a case by case basis
    • Always admit if pregnant, patient uses a pump or IV insulin, intentional insulin overdose
    • Sulfonylureas are slow to be excreted, so admit patients on these if they become hypoglycaemic, don’t dischrage from ED
    • Admission often best if patient has a history of hypoglycaemic unawareness, prolonged hypoglycaemia, is a frequent attender with hypoglycaemia, is frail or is now unable to manage diabetes without help

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Consider the cause / risk factors (and help prevent it recurring)

• Insulin issues
  • • Using stat doses of short acting insulin (correction doses)
    • Prescribing errors – incorrect insulin given, or at incorrect concentration or incorrect units administered (check if it was the right dose, the right insulin, at the right time)
    • Administering errors – such as using the wrong syringe
    • Stopping steroids, or recovery from an acute illness and not readjusting the insulin dose
    • Changing insulin injection site or history of lipodermohypertrophy
    • No IV glucose given alongside IV insulin (eg in DKA)
    • Self-harm / factitious / poisoning
    • Incorrect insulin to carbohydrate ratio used
• Intake and output issues
  • • Patient kept nil-by-mouth (eg pre-operatively)
    • A patient not eating, eating less or with an eating disorder
    • Vomiting
    • Exercise
• Medical history and patient characteristics
  • • Previous inpatient hypoglycaemia – the biggest risk factor for another, probably confers > 5% risk of another one in the next year
    • Poor CBG monitoring / strict control / fear of hyperglycaemia
    • Hypoglycaemia unawareness
    • Early pregnancy and breastfeeding
    • GI disease – malabsorption, previous bariatric surgery, gastroparesis
    • Frailty / dementia
    • CKD
• Acute medical issues
  • • AKI
    • Sepsis / critical illness
    • ETOH use or liver disease
    • Endocrine disorders (especially if undiagnosed) – Addison’s, growth hormone deficiency, hypothyroidism, hypopituitarism, insulinoma
    • Post limb amputation
    • The presence of insulin binding antibodies
• Other medications
  • • Medications used in CV disease – warfarin, betablockers, fibrates
    • Antibiotics – linezolid, co-trimoxazole, ciprofloxacin and especially levofloxacin
    • Medications that interact with sulfonylureas by increasing their effective dose – clarithromycin, co-trimoxazole, metronidazole, fluconazole
    • SSRIs
    • Other – quinine, salicylates (in high dose), NSAIDs, somatostatin analogues, pregabalin, pentamidine, IGF, ritodrine
    • Stopping steroids

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Consider taking bloods

• HbA1C – but interestingly the risk of a severe hypoglycaemia is pretty much the same across all HbA1c levels (high HbA1c and low HbA1c have similar risk)
• Lab glucose – pseudohypoglycamia can occur in poorly perfused / shocked patients, or if polycythaemic
• LFTs
• ETOH level
• Salicylate level
• Serum save
• Cortisol
• Insulin level and C-Peptide (if high, suggests endogenous insulin, if low, exogenous)
• Urine sample for sulfonylureas if you suspect poisoning

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Other measures

• Consider adjusting treatment – consider stopping sulphonylureas (especially if patient is old/frail) and adjusting insulin dose (see insulin)
• Consider giving IV glucose if risk of hypoglycaemia likely to be prolonged
• Organise diabetes specialist nurse review
• Educate about hypoglycaemia prevention – this saves lives
• Consider incident report (eg datix) for inpatient hypoglycaemia
• Review injections sites
• Consider commencing Continuous Glucose Monitoring if higher risk (but at least ensure they have a CBG machine and strips)
• Restock hypoglycaemia box if utilised on ward
• Patients should adjust their pump settings if they have one
• Advise to eat more carbs than usual with next meal
• Management if any hypoglycaemia unawareness
  • • Educate family / carers
    • Ensure glucagon at home
    • Consider adjusting target HbA1c (but usually not advised to do so)
    • Consider pump or CGM (with alarms settings)
    • Rarely patients referred for pancreas transplant
• Prescribe glucagon IM for anyone leaving hospital if admitted with a severe hypo
  • • Teach relatives / carers how to administer
    • Only 10% of patients eligible are discharged with it
    • Can be a bit of a faff to make up before injection
    • Ogluo prefilled glucagon is much easier, available as a private prescription for 70 quid.
    • Can also give Baqsimi nasal glucagon (but not available in UK currently)

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Driving advice

• Check current guidance and advise accordingly (see DVLA rules)
• Normal drivers can continue if they
  • • Have adequate hypoglycaemic awareness if takling insulin (CGM alarms are not a substitute)
    • Have no more than one episode of severe hypoglycaemia whilst awake in the last 12 months (and most recent episode must have occurred > 3 months ago)
    • Monitor CBGs appropriately and eyesight is adequate
    • Are under regular review for their diabetes
• HGV/lorry/bus drivers
  • • Need full awareness
    • Must stop driving immediately if one severe hypoglycaemic episode in the last 12 months
    • Must monitor CBGs and store readings for > 6 weeks