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Managing Inpatient Glycaemia Dr Sue Lynn Lau Diabetes Clinical Workshop Newcastle October 2011 Case 1 - Doug • 55 year old overweight male • Admitted overnight with chest pain, ST changes on ECG • Background history • Hypertension • Hypercholesterolaemia • Benign prostatic hypertrophy • Medications • Irbesartan 150mg • Atorvastatin 40mg Case 1 - Doug • No previous history of diabetes • Random BGL in ED was 14 mmol/L, no treatment • Next morning the formal fasting BGL is 8.4 mmol/L. Case 1 - Doug • Does Doug have diabetes? • What is your management plan • acutely? • on discharge? Case 2 - June • 72 year old female presents with fever, productive cough, dyspnoea. • Sats 91%, WCC 16, Creat 140, CXR – RLL consolidation • Commenced on intravenous antibiotics • Background • Type 2 DM for 7 years • Smoker • Hypertension • Osteoarthritis Case 2 - June • Lives alone, but independent and active. • Medications • Metformin 1g bd • Gliclazide MR 60mg daily • Amlodipine 5mg • Anti-inflammatories Case 2 - June BGLs on the ward after 1 day • 6 am – 10.3 mmol/L • 11.30 am – 16 mmol/L • 5.30 pm – 12. 4 mmol/L • 9 pm – 15.1 mmol/L • What do you advise? - stat dose of 4 units NR Case 3 - Mike • 25 year old male with Type 1 diabetes since age 13. • Fractured ankle after MVA, on ortho ward following operation fixation. • Novorapid 6 units tds, Levemir 24 units nocte • 4 days post-op, he is found sweaty, pale and confused in bed at 3pm. BGL 1.5 mmol/L. • What next? Inpatient glycaemia 1. Stress hyperglycaemia 2. Why treat hyperglycaemia in hospital? 3. What are the glycaemic targets of a hospitalised patient? 4. Management strategies for inpatient hyperglycaemia • how to use insulin • what to do with oral hypoglycaemics 5. Management of inpatient hypoglycaemia Stress Hyperglycaemia physiological stress infection, myocardial infarction, stroke, trauma Hormones ‘counterregulatory’ factors catecholamines, cortisol, glucagon β-cell stress Inflammatory cytokines TNF-α Insulin-resistance hyperglycemia Stress Hyperglycaemia • ‘Stress Hyperglycaemia’ - elevated BGL (eg >11.1 mmol/l or >7 mmol/L) - in the context of systemic illness - without pre-existing diabetes. • Difficult to define Stress Hyperglycaemia • • • • Some use HbA1c > 6.1% or >6.5% to define preexisting but undiagnosed diabetes HbA1c doesn’t capture all pre-existing diabetes Recent high BGL related to stress may contribute to elevated HbA1c. HbA1c pitfalls in hospitalised patients Stress Hyperglycaemia • Very Common − Levetan et al. Diabetes Care 1998 • Survey of 1034 hospitalised patients • >1/3 had BGL documented > 11.1 mmol/L • only 7% had diabetes as a diagnosis in notes. - Umpierrez et al. JCEM 2002 • 2000 patients admitted to general medical ward. • 7% had no BGL measured at any stage • Of the rest, 26% had previous history of diabetes • 12% had newly diagnosed hyperglycaemia Stress Hyperglycaemia • Does it matter? IN HOSPITAL MORTALITY known diabetes 3% new hyperglycaemia 16% p<0.01 • normoglycaemia 1.7% p<0.01 Cause or Association? • • • Does high BGL have detrimental effect? Is high BGL just a marker of more severe illness? 42% received insulin, mostly sliding scale vs 77% in diabetic group. Stress Hyperglycaemia • Does it matter? - More like to die if your admission BGL is high • AMI, CVA (3-4 times risk of death) * - Cheung et al, Diabetologia 2008 • 6187 consecutive ED patients • Admission BGL correlated to mortality * Capes et al. Lancet 2000 Capes et al. Stroke 2001 Stress Hyperglycaemia • Does treating hyperglycaemia improve outcomes? - Theoretical benefit • Hyperglycaemia alters immune function, cell death, oxidative stress, endothelial dysfunction, thrombosis, inflammation ⇒ increased infections ⇒ poor healing ⇒ increased infarct size after AMI Stress Hyperglycaemia • Does treating hyperglycaemia improve outcomes? - Several trials in different situations – ICU, AMI, Stroke Some positive results • decreased deep wound infection • decreased mortality • decreased length of stay Stress Hyperglycaemia • Does treating hyperglycaemia improve outcomes? - Others find no benefit • May depend on the target BGL set • How well they achieved target vs control group • Rates of hypoglycaemia • Suggestions of detriment if target BGL is too low. Stress Hyperglycaemia • What are our treatment targets? - American College of Endocrinologists and Australian Diabetes Society • Critically ill – infusion target 7.8 - 10 mmol/L • Non-critically ill – target <7.8 fasting, <10 random • not less than 5 mmol/L Doug • • • 55 yo male with chest pain BGL 8.4 mmol/L fasting, 14.0 mmol/L random. No previous history of diabetes • SUGGESTIONS? Doug- Scenario 1 • • • Ring pathology lab for previous results – fasting BGL of 6.8 mmol/L in 2006. HbA1c 7.8% Doug’s chest pain resolves, ECG remains unchanged and his serial cardiac enzymes are not elevated, planned for discharge and outpatient follow-up. Doug – Scenario 1 • • • • • • Referred to the diabetes educator and dietician. Commences home blood glucose monitoring. Metformin 500mg bd initiated, increased to 1g bd after 1 week. With increased physical activity and attention to diet, he loses 3kg over the next 3 months. Fasting BGLs are down to 5 mmol/L and post-prandial readings all <10 mmol/L. An HbA1c 3 months later is 6.5%, he continues metformin and stops home BGL monitoring. Doug – Scenario 2 • • • • Ring Path lab – fasting BGL was 5.2 mmol/L in 2006. HbA1c is 5.9% He has a further episode of chest pain with ST depression in the anterior leads and his troponin levels rise. He is planned for angiography as an inpatient. • SUGGESTIONS? Managing Inpatient Hyperglycaemia • Options for treatment of hyperglycaemia - - Intravenous Insulin infusion Subcutaneous insulin Sliding scale insulin (short acting given on PRN basis when BGL rises, dose titrated according to BGL) basal bolus (long-acting daily, short-acting with meals) pre-mixed short+long acting, twice a day. Oral hypoglycaemic agents Managing Inpatient Hyperglycaemia • Intravenous insulin infusions Achieves glycaemic control quickly Can adapt to changes in patient’s condition. Requires minimal endocrinological expertise as long as protocol is clear and strictly followed. Insulin absorption not an issue Good in fasting patients, less easy if eating. x x x x Frequent BGL testing for patient IV access issue. High use of nursing resources Some experience required Appropriate in critically ill patients managed in ICU/HDU setting, surgical patients, Type 1, difficult/unstable BGL. Managing Inpatient Hyperglycaemia • Sliding Scale Insulin – short-acting insulin - • Eg, BGL 8 – 12 BGL 12.1 – 16 BGL 16.1 – 20 BGL >20.1 = = = = Give 2 units Give 4 units Give 8 units Give 10 units, call M.O. Issues - Which short-acting to use? - How often to administer, pre-meals/post-meals/overnight? - Adjusting scale for different levels of insulin resistance Managing Inpatient Hyperglycaemia • Sliding Scale Insulin - Easy to use and to chart Easily ignored and unused, even if charted Responds to high BGL but does not prevent them “reactionary” vs “proactive” Greater swings, BGL instability Hypos, especially with insulin stacking Rebound phenomena GENERALLY AVOIDED IF POSSIBLE Managing Inpatient Hyperglycaemia • Regular subcutaneous insulin - Basal Bolus + supplemental, eg Lantus nocte, Humalog TDS with meals + extra Humalog if BGL high. Managing Inpatient Hyperglycaemia • Regular subcutaneous insulin - Pre-emptive Dose titrated based on previous days readings Flexible, can be used in patient with minimal or variable oral intake. Can be taught to staff with minimal endocrine experience Achieves better glycaemic control and stability than SSI. Takes about 3 days to achieve target of 7-8 mmol/L Managing Inpatient Hyperglycaemia Calculate a total daily dose (TDD) based on body weight and patient characteristics ( table below for insulin-naïve patients), then split the TDD into 50% basal and 50% bolus (divided into 3 meals) TDD Estimation Patient Characteristics 0.3 units/kg body weight Underweight Older age Hemodialysis 0.4 units/kg body weight Normal weight 0.5 units/kg body weight Overweight >0.6 units/kg body weight Obese Insulin resistant Glucocorticoids Managing Inpatient Hyperglycaemia • • • • • • • Tailor to patient’s glycaemic pattern. Assess and titrate the doses daily Adjust long-acting dose to target fasting BGL Adjust short-acting dose to target the increment in BGL from pre to post-meal. Consider how much supplemental dose was required on the previous day. Dose adjustments of 10-20%, depending on how far off target. Does not commit patient to long term insulin therapy Managing Inpatient Hyperglycaemia • BD mixed insulin - Less flexibility, patient committed to eat certain amounts at certain times. - Inappropriate in ill, unstable patient. - Useful in relatively well patient, normal diet, soon to be discharged, not planning basal bolus use in community. Managing Inpatient Hyperglycaemia • Oral hypoglycaemics - Metformin unsuitable in seriously ill with poor perfusion, renal impairment, IV contrast - Sulphonylureas unsuitable if poor oral intake, other risk factors for hypoglycaemia - Glitazones risky in fluid overload/CCF - Delayed onset and offset of action - May be used/continued in stable patient, normal appetite, soon to be discharged, not planning insulin therapy in community. June • 72 yo female with pneumonia, renal impairment, sepsis • Known Type 2 DM on max. dual oral hypoglycaemics • BGL profile • 6 am – 10.3 mmol/L • 11.30 am – 16 mmol/L - stat 4 units NR • 5.30 pm – 12. 4 mmol/L • 9 pm – 15.1 mmol/L QUESTIONS/SUGGESTIONS? June – Scenario 1 • Weight 56kg, Height 160cm • Feels nauseous, but eating • Home BGL monitoring, fasting BGLs 6 - 8 mmol/L • No hypos • HbA1c 7.5% • Normal renal function 3 months ago • Urine albumin/creatinine ratio 1.3 mg/mmol (normal) • No evidence of retinopathy, neuropathy June – Scenario 1 • Ceased metformin and glicazide • Commence Glargine 12 units nocte, Lispro 4 units immediately after eating if tolerates meal. • Supplemental scale tds before meals and before bed - BGL 10 – 12 mmol/L 2 units 12.1 – 16 mmol/L 4 units 16.1 – 20 mmol/L 8 units • Discharge planning - diabetes educator review, discussed short-term use of insulin, taught insulin administration. June – Scenario 1 • June improves with IV antibiotics • Creatinine returns to baseline • After 3 days, the oral hypoglycaemics are restarted • The insulin dose is initially up-titrated, then downtitrated with the reintroduction of OHG, able to cease bolus (meal-time) insulin. • Discharged on Glargine + metformin + gliclazide with outpatient follow-up. • Plan for self-titration of Glargine depending on fasting BGL. June – Scenario 2 • Weight 56kg, Height 160cm • Feels nauseous, but eating • Home BGL monitoring, fasting BGLs 9 - 10 mmol/L • No hypos • HbA1c 8.5% • Hasn’t seen a regular LMO for some years • Not screened for complications June – Scenario 2 • Oral hypoglycaemic agents ceased • Commenced on basal bolus insulin + supplemental dosing, doses titrated daily. • Creatinine stabilises at 90 umol/L • Discussed use of long-term insulin therapy on discharge • Metformin cautiously re-introduced at 500mg bd • Once eating reliably, basal bolus switched to pre-mixed bd regimen. • Education re: home BGL monitoring, complication screening, hypoglycaemia management, dietary needs. Case 3 - Mike • 25 yo male, long-standing Type 1 diabetes. • 4 days post orthopaedic surgery • Novorapid 6 units tds, Levemir 24 units nocte • He is found sweaty, pale and confused in bed at 3pm. BGL 1.5 mmol/L. • What next? Hypoglycaemia in hospital • Factors contributing to hypoglycaemia in hospital - poor appetite and intake, vomiting - fasting for procedures - delay in meal-times - breaks in enteral feeding - renal dysfunction - reintroduction of physical activity – physio/OT - overzealous insulin administration -corticosteroid use - patient unable to self-report symptoms Hypoglycaemia in hospital • Does it matter? - Critically ill patients • increased risk of death, seizures • NICE-SUGAR – do not target normoglycaemia when using insulin infusion in ICU. • Excess deaths appear to be cardiovascular Hypoglycaemia in hospital • Does it matter? - Non-critically ill patients • Turchin et al, Diab Care 2009 • Hypoglycaemia in 7% of diabetic admissions • Hypoglycaemia associated with increased length of stay (2-3 days), inpatient mortality, mortality at 1 year. - Associational, is it a marker of more severe illness? Management of hypoglycaemia • Acute management – recommended clinical cut-off for hypoglycaemia is <4 mmol/L, individual symptoms vary. •Conscious patient • 15g carbohydrate orally •5-7 jelly beans •150 mls soft drink or juice (not diet) •100mls Lucozade •Glucose tablets (equivalent to 15g) •3 teaspoons of sugar • Recheck in 15 minutes, if BGL not rising, repeat Management of hypoglycaemia • Acute management •Conscious patient • If next meal is >20 min away, add longer-acting carbohydrate • Sandwich, glass of milk, piece of fruit, 1 tub of yoghurt, 6 small dry biscuits and cheese Management of hypoglycaemia • Acute management • Patient with impaired consciousness • If IV access available, quickly achievable • 50 ml of 50% dextrose (25g glucose) • or 25 ml of 50% dextrose (12.5g glucose) • trials looking at 10% dextrose in 50 ml (5g) increments. • No IV access achievable, glucagon 1mg s/c or IM Management of hypoglycaemia • Subsequent management - what precipitated the episode? - subsequent risk of hypoglycaemia in next 24 hours - adjust insulin dosing appropriately - never withhold long-acting insulin because of hypoglycaemic episode. Mike • Resuscitated with intravenous 50% glucose, followed by a sandwich once he regains consciousness. • Chart review – BGL has been dipping in the afternoons over last few days. • Patient history – Mike wasn’t keen on today’s lunch, mobilising more with crutches this afternoon. • BGL at home – erratic. Has noticed BGL of 2.0 mmol/L without symptoms. • Examination – some areas of lipohypertrophy on abdomen and upper thighs. Mike • Mike’s insulin doses are reviewed and decreased appropriately. • More frequent BGL monitoring overnight. • Sees diabetic educator – revises hypo management, insulin administration. • Dietician, refresher on carbohydrate counting. • Advised to maintain BGL > 6 mmol/L • Advice about driving • Mike’s partner shown how to use glucagon kit Take Home Messages • Hyperglycaemia is common in hospitalised patients, many without previous knowledge of diabetes. • HbA1c may help to distinguish those with undiagnosed diabetes, likely to require long-term therapy. But beware pitfalls. • New hyperglycaemia is a marker for worse outcome and should be treated as for diabetic patients. Take Home Messages • Insulin is the most appropriate therapy in acutely ill patients, consider temporary cessation of OHG • Target BGL <10 mmol/L and not less than 5 mmol/L • Insulin infusions useful in the critically ill and fasting. • Regular sc insulin (Basal+bolus+supplemental) better than sliding scale, low risk of hypoglycaemia if targets appropriate. Take Home Messages • Be aware of increased risks for hypoglycaemia in hospital, avoid overzealous glycaemic targets. • Follow hospital protocol for hypoglycaemia management, do not overtreat, do not withhold longacting insulin. • Look for precipitating factors in your individual patient. Take Home Messages • Hospitalisation is a good opportunity to (re)educate and (re)motivate patients towards better diabetes management. • Discharge planning should begin early and involve the endocrine team, dietician and diabetes educator. • Requirements may change quickly after discharge, outpatient follow-up and liaison with GP is essential.