Inpatient Diabetes and Hyperglycaemia Philip Dyer Heart of England NHS Foundation Trust Birmingham
A Case of Inpatient Diabetes 22.09.15 Mrs DE Ketosis-prone T2DM on bd Humulin-I, Metformin and Linagliptin Admitted with a fall 19:00h nursing note - patient declined most of her evening meal 23.09.15 02:00h Dr called to review CBG 1.1 mmol/l FY1 note given IM Glucagon, ½ Glucogel and 100mL 10% Glucose - CBG 13.0 mmol/l Stop IV Glucose and monitor CBG hourly 23.09.15 11:00h JD WR Events overnight noted very low BGs, BGs and. Having frequent hypos. Earlier in the week agreed to sheltered accommodation. No recollection of this. Plan reduce Humulin-I by 4 units Speak to Diabetes consultant Arrange best interest meeting
25.09.15 05:30h Nursing note - CBG 3.0 mmol/l A Case of Inpatient Diabetes Given Glucogel, cup of tea and 2 biscuits Recheck CBG 5.0 mmol/l 25.09.15 11:00h JD WR Applying for guardianship BGs high on admission may have not been taking Metformin and Linagliptin HbA1c between 9.4-11.8% since 2013 Note severe hypo on 23.09.15 Not had insulin since the 23.09.15 HbA1c (%) eag (mmol/l) 5 5.4 6 7.0 7 8.6 8 1.2 9 11.8 10 13.4 11 14.9 12 16.5 Plan stop insulin, PRN Novorapid if required, target HbA1c 9-10% comfortably as all we need to do is limit hyperosmolar symptoms and stop dangerous hypos.
A Case of Inpatient Diabetes 26.09.15 13:10h Nursing note - BGs Hi, ketones 6.0 mmol/l SHO advice 4 units Novorapid 13:30h BGs - Hi, ketones 5.5 mmol/l 16:00h FY2 review Repeat ketones now 2.6 mmol/l Patient had been drinking Lucozade which caused the spike Plan due to receive Metformin Repeat CBG at 1830h Give 5 units Novorapid for one off high BGs Ketones though high responded to Novorapid and with her present state and non-compliance I see it not with starting on sliding scale 22:00h FY1 review Currently BG unrecordable and ketones 1.7 mmol/l Plan repeat Novorapid 4 units and recheck ketones, please contact if >0.6 mmol/l
A Case of Inpatient Diabetes (continued) 27.09.15 28.9.15 Consultant WR CBGs was 33 over the weekend. Had 3 bottles of Lucozade. CBG coming down. Patients looks well. Plan await court of protection and continue current treatment of Novomix (meant Novorapid) 29.09.15 11:00h DADOT review AMT4 = 0, Attention obviously altered, very drowsy but rousable. Acute event is evident 4AT = 8, Delirium is evident 29.09.15 13:15h Nursing note Appears to be getting more confused BGs 33.1 mmol/l and ketones 7.1 mmol/l Dr informed Actrapid 4 units given For IV sliding scale 14:00h CT1 note Patient vomiting O/E MEWS = 2 and mild epigastric tenderness Imp DKA
Mrs DE Glycaemic Control during her Admission
Does Glycaemic Control Matter? Hyperglycaemia is important
Does Glycaemic Control Matter? Hypoglycaemia is important
Summary of hypothetical relationship(s) between hyperglycaemia and adverse outcomes in patients with ACS and posited mechanisms of the beneficial effects of insulin. Intravenous Insulin Christina H. Wei, and Sheldon E. Litwin Diabetes 2014;63:2209-2212
Update on Mrs DE Admitted 6 weeks later with AMI
What should the inpatient blood glucose target be?
Insulin Secretion The Basal Bolus Concept Insulin Component Basal Bolus Properties Near-constant insulin level throughout the day Suppresses hepatic glucose production (glycogenolysis and gluconeogesis), proteolysis and lipolysis. Insulin requirement to suppress hepatic glucose production overnight and between meals. Covers ~50% of the total daily insulin requirement Reflects BG overnight, before breakfast and before meals if there is a 5- hour gap. Immediate rise and sharp peak at 1-hour Limits post-meal hyperglycemia Insulin requirement to maintain normal glucose disposal after eating Cover ~50% of the total daily insulin requirement (10-20% at each meal) Reflects BG 2-hours after meals
Bolus/prandial insulin is necessary for maintaining blood glucose control, after food (prevents post prandial hyperglycaemia). Therefore basal insulin is continuous insulin secreted between meals and bolus/prandial insulin is secreted in burst in response to eating. How would we manage without basal insulin? Because the liver is secreting glucose into the bloodstream continuously, a complete lack of insulin, would result in a sharp rise in blood glucose level (2.5 mmol/l/h). Without basal insulin, cells would resort to burning only fat for energy, and produce ketones. Continuous insulin = basal insulin and switches off ketogenesis and ensures cells get energy between meals. How would we manage without bolus/prandial insulin? Without bolus/prandial insulin, we are unable to control post prandial glucose.
Insulin Requirement When Unwell
Insulin Regimes for Hospital TYPE OF INSULIN Name What is it Indications Starting TDD Dose BACKGROUND/BASAL INSULIN Glargine (Lantus) Levemir (Detemir) Insulatard or Humulin-I Consists of a long-acting insulin preparation administered regardless of the patient s oral intake status, with the premise of matching hepatic (endogenous) glucose production Not controlled on oral multiple anti-diabetic agents. Course of treatment for specific indication e.g. starting steroids, oral antidiabetic agents suspended. 0.3 units/kg E.g. 80 kg = 0.3 x 80 = 24 units. PRANDIAL/BOLUS INSULIN BASAL BOLUS REGIME PRE-MIXED TWICE DAILY INSULIN Novorapid Combination of basal Novomix 30 Humalog insulin and rapid acting Humalog Mix 50 Glulisine analogue insulin. Humalog Mix 25 Rapid-acting Long-acting basal insulin Pre-mixed analogue insulin administered regardless combination of preparation given to of the patient s oral intermediate acting cover nutritional intake status and rapidacting and rapid acting needs. analogue insulin analogue insulin. preparation given to cover nutritional needs. In combination with basal insulin e.g. basal plus or basal bolus. 0.1 units/kg E.g. 80 kg = 0.1 x 80 = 8 units For tight glycaemic control and flexible regime. 0.5 units/kg E.g. 80 kg = 0.5 x 80 = 40 units. Basal = 50% Bolus =50% Basal = 20 units Bolus = 7 units tds Poor glycaemic control on anti-diabetic agents or basal insulin only not wanting four injections. 0.5 units/kg E.g. 80 kg = 0.5 x 80 = 40 units SUPPLEMENTAL OR CORRECTION INSULIN Novorapid Humalog Glulisine Rapid-acting analogue insulin To correct capillary blood glucose (CBGs) values that exceed predetermined targets. T1DM 1 unit to lower CBG by 2.0 mmol/l T2DM 0.1 unit/kg Consider lower dose in frail elderly, CKD stage 4/5 e.g. 0.2 units/kg for basal insulin and higher doses in obese, on steroids or HbA1c >9.0% (75 mmol/mol) e.g. 0.6 units/kg for pre-mixed insulin.
Insulin Regimes for Hospital TYPE OF INSULIN BACKGROUND/BASAL INSULIN PRANDIAL/BOLUS INSULIN BASAL BOLUS REGIME PRE-MIXED TWICE DAILY INSULIN SUPPLEMENTAL OR CORRECTION INSULIN Do you continue when not eating What percentage of the TDD to give when not eating What do when unwell Monitoring required to adjust insulin dose Yes, may require a reduced dose No, as patient is not eating Yes, but at 50% of the TDD OR convert to basal insulin only at 50% of their TDD 100% of the TDD None 100% of the basal 50% Variable Basal insulin requirement may remain constant or often increase. Pre-breakfast (fasting) and pre-evening meal CBG. Depending on whether the patient is eating or not the bolus insulin requirement may increase or decrease 2-hours post meal BG Same as for basal and prandial insulin. Pre-mixed doses may need to increase Pre-breakfast (fasting) and pre-evening meal BG.. Used only to correct CBGs which are above target. Correction doses of insulin may be required to maintain good glycaemic control. If repeated correction doses are required the current regime should be reviewed, probably requiring an increase. Variable
Commence New Antidiabetic Medication. When CBG<12.0mmol/L start: 1. Basal Bolus Insulin for T1DM or ketosis prone T2DM - Total daily dose (TDD) - 0.5 units/kg 2. Basal Only Insulinfor T2DMs on 3 different tablets or 1 or 2 tablets and CBG 14.0mmol/L. - TDD - 0.3 units/kg. Continue all the tablets. 3. Premixed Additional Twice new daily class Insulin of antidiabetic 0.5 units/kg. tablet Continue if 1 Metformin 2 tablets stop and all CBG<14.0 other tablets. mmol/l(page 1.) Basal Bolus Regime Rapid acting insulinse.g.humalog or Novorapid Long acting Insulinse.g. Lantus orlevemir For Basal Only Regime Long acting Insulinse.g.Lantus, Levemir or Insulatard Starting Insulin Give 50% of total dose with evening meal in the form of long acting insulin and divide the remaining dose equally with meals for rapid acting insulin Meal Breakfast Lunch Evening Bedtime Rapid acting 6 units 6units 6 units Long acting 18 units Give 50% of total dose with evening meal in the form of long acting insulin and divide the remaining dose equally with meals for rapid acting insulin Meal Breakfast Lunch Evening Bedtime Lantus 22units Levemir 22 units Insulatard 11 units 11 units E.g. Weight 72 Kg, starting total daily dose (TDD) 0.5 x 72 = 36 units. E.g. Weight 72 Kg, starting total daily dose (TDD) 0.3 x 72 = 22 units. NOTE: Pre-mixed BASAL Insulin INSULIN MUST BE GIVEN MealPRIOR TO Breakfast DISCHARGE OTHERWISE Lunch AFTER 4 HOURS Evening THE PATIENT Bedtime WILL NOT HAVE ANY INSULIN ON BOARD AS THE RAPID ACTING INSULIN WOULD HAVE RUN OUT. Novomix 30/Humalog 24 units 12 units Mix 25/Humalog Mix 25 CRITERIA FOR DISCHARGE All are necessary for a safe discharge 1. Able to monitor& record CBG independently 5. Capillary Ketones <0.6 mmol/l 2. Able to administer insulin independently 6.CBG 10.0 mmol/l 3. Access to a telephone Able to attend a follow up appointment in the Diabetes Centre x42034 Fax 40420 E.g. Weight 72kg, starting TDD 0.5 x 72 = 36 units
What to do if the patient is not eating? Mrs A is a type 1 diabetic on a basal bolus regime Breakfast Lunch Evening Meal Bed Humalog 8 10 12 Glargine 30 He presents with symptoms consist with pyelonephritis fever, loin pain, dysuria and a urine dipstick positive for leucocytes and nitrites. Investigations - WCC 24.7, CRP 212 and CBG 8.4 mmol/l. He is feeling nauseous and does not feel like eating What do you do to control his BG? Answer - Continue Glargine and suspend Humalog while not eating Breakfast Lunch Evening Meal Bed Humalog 0 0 0 Glargine 30 Mr C is a type 2 diabetic on a premixed bd insulin regime Breakfast Lunch Evening Meal Bed Novomix 30 32 20 He presents with diarrhoea. He is fluid resuscitated and started on replacement and with 0.9% NaCl with KCl. CBG is 6.4 mmol/l and capillary ketones 0.1. He does not feel like eating What should be done with his insulin regime to control his BG? Continue current regime at 50% of the usual dose Breakfast Lunch Evening Meal Bed Novomix 30 16 10
How to give a Correction Dose
How to Calculate the dose and When to Recheck CBG? Type 1 Diabetes* Assume that 1 unit will drop capillary blood glucose (CBG) by 2.0 mmol/l, to a maximum dose of 10 units initially. Aim to correct to 8.0 mmol/l E.g. if CBG was 28.0 mmol/l, 28.0-8.0 = 20.0, 20.0 2 = 10, therefore give 10 units. Type 2 Diabetes* Give 0.1 units/kg of insulin to a maximum dose of 10 units initially. Example 100 kg patient = 100 x 0.1 = 10 units *Wherever possible take advice from the patient about the amount of insulin normally required to correct a high blood glucose (Correction or Insulin Sensitivity Factor) 1st check - 2-hours At peak effect. Is it coming down? 2 nd check - 4-hours Glucose lowering effect almost complete. Decision on further Rx reqd
How to Manage Inpatient Diabetes and Hyperglycaemia
Now for some cases!!
Case 1 Self referral to ED. 54 year old Asian male with T2DM. Presented with hyperglycaemia. On examination she was afebrile, pulse 82 regular, BP 134/76, RS clinically clear, weight 85 kg. Current Regime Breakfast Lunch Evening meal Bedtime Metformin 1g 1g Gliclazide 80mg 80mg Sitagliptin 100mg The laboratory data showed: Na+ 138 mmol/l (137 144) WCC 5.4 (4.0-11.0) K+ 4.9 mmol/l (3.5 4.9) Hb 155 (115-165) Urea 8.6 mmol/l (2.5 7.0) Plts 300 (150-450) Cr 88 mmol/l (60 110) CRP 12 (<10mg/dL) Capillary blood glucose 18.4 mmol/l Capillary ketones 0.4 mmol/l (<0.6) HbA1c 9.4% (79 mmol/mol) What is the diagnosis? Hyperglycaemia
How would you manage Case 1? 1. Correction dose of rapid acting insulin such as Humalog. 0.1 unit/kg 85 x 0.1 = 8.5, therefore give 8.0 units 2. Start basal insulin - Humulin-I 0.3 units/kg = 0.8 x 85 = 25.5, therefore 26 units Breakfast Lunch Evening meal Bedtime Humulin-I 13 units 13 units 3. Recheck CBG and ketones in 2 hours - If CBG <12.0 mmol/l and capillary ketones < 0.6 mmol/l, the patient can be discharged. - If CBG >12.0 mmol/l give a 2 nd correction dose and repeat CBG and capillary ketones in 2 hours. Criteria for discharge, same as above. 4. Give 500-1000ml of Hartmanns over 2 hours to correct the dehydration and help lower CBG 5. Continue all their other oral anti-diabetic medications 6. Contact Inpatient Diabetes Team to organise education on insulin administration, CBG monitoring and the treatment of hypoglycaemia.
Case 2 A 19-year-old single diabetic Caucasian woman had been on 22 units of Lantus and 8 units of Novorapid before meals daily for six years. She presented at the ED with nausea and malaise of a 1 day duration. Polyuria, polydipsia and altered CBG values had been present for approximately one month, but were overlooked by the patient. The laboratory data showed: Na+ 134 mmol/l (137 144) K+ 4.7 mmol/l (3.5 4.9) Urea 7.2 mmol/l (2.5 7.0) Cr 72 mmol/l (60 110) Capillary blood glucose 22.4mmol/L Capillary ketones 2.1 mmol/l (<0.6) Venous Gas ph 7.35 (7.35-7.45) HCO3 24.0 (24-28) K+ 4.7 (3.5 4.9) Cl 104 (95-105) Lactate 0.9 mmol/l (0.3 1.3) Anion gap 8 (8-12) What is the diagnosis?
Management of Mild DKA with Subcutaneous Rapid Acting Insulin Management of DKA with Subcutaneous Rapid Acting Insulin Indications - Patients with mild ketosis and acidosis Criteria -Type 1 or Type 2 Diabetes - CBG >14.0 mmol/l - capillary ketones 1.5-2.9 mmol/l - ph 7.25 Type of Insulins to be used Novorapid/Humalog/Glulisine Resolution of ketosis = capillary ketones <0.6 mmol/l Resolution of hyperglycaemia = CBG <12.0 mmol/l If not confident treat as DKA Intravenous Fluids Potassium Replacement Insulin Therapy Subcutaneous Insulin 2 hourly Laboratory 1. 0.9% sodium chloride (NaCl) at 500-1,000ml/h for 2 h 1. If serum K + 5.5mmol/L, do not give K,, but check serum K every 2 h a) Initial dose SC: 0.1-0.2 units/kg OR 1 unit to lower CBG by 2.0 units followed by Admission: FBC, U&Es, Glc, venous gas for ph and bicarbonate and K + 2. 0.45% NaCl at 250-500ml/h until blood glucose 14.0mmol/L 2. If K + 4.0-5.5 mmol/l, add 20 mmol of KCl to each litre of IV fluid b) SC rapid-acting insulin at 0.1-0.2 units 2 hours later and then Capillary Glucose: Check glucose every hour 3. When blood glucose <14.0mmol/L use NaCl 0.18%, Glucose 4% at 150 250 ml/h until resolution of ketosis 3. If K + 3.0-4.0mmol/L, add 40 mmol of KCl to each litre of IV fluid c) SC insulin 0.05-0.1 unist/kg every 2 hours to keep glucose at 12.0mmol/L until resolution of ketosis. Capillary Ketones (bhydroxybutyrate): Check ketones every hour 4. If K + <3.0 mmol/l, give 10-20 mmol of KCl per hour until serum K + >3.0 mmol/l, then add 40 mmol of KCl to each litre of IV fluid Venous Gas for ph and bicarbonate and K + every 2 hours
Case 3 A 73 year old woman with T2DM is referred to the AMU from the ED. She has been unwell with thirst, dysuria and urinary frequency for 3 days. On examination she was drowsy with a Glasgow Coma Scale of 9. Blood pressure is 104/76mmHg, pulse 126 bpm and irregular. Capillary blood glucose is reading high. The laboratory data showed: Na+ 139 mmol/l (137 144) K+ 5.6 mmol/l (3.5 4.9) Urea 19.2 mmol/l (2.5 7.0) Cr 189 µmol/l (60 110) Serum glucose 41.1 mmol/l (3.5-6.0) Arterial Blood Gas (on air) ph 7.41 (7.35-7.45) po 2 10.9 kpa (10.5-13.5) pco 2 4.9 kpa (4.6-6.0) bicarbonate 22.2 mmol/l (24-28) base excess 0.8 mmol/l (±2) Calculated Serum Osmolality 2(Na + K) + Urea + Glc = 349.4 Or (2Na + Glc + Urea) = 338.3 Hyperosmolality >320
How to manage Case 3 INTRAVENOUS fluids 0.9% NaCl to correct circulatory volume and dehydration. Only switch to 0.45% NaCl if the osmolality is not declining An initial rise in Na + is expected Do Not give 0.45% NaCl. The rate of fall of Na + should not exceed 10.0 mmol/l in 24 hrs INSULIN INFUSION Start ONLY if CBG fails to fall with IV fluids Half the DKA calculated dose (0.05 unit/kg/hour) The fall in CBG should be no more than 5.0 mmol/l/hr ANTICOAGULATION Full dose anticoagulation dose unless contraindicated. DISCHARGE ANTIDIABETIC TREATMENT All patient should be discharged on INSULIN not oral agents.
DKA Cannula Port 1 Cannula Port 2 INTRAVENOUS 0.9% SALINE Aim/Function: 1. Fluid resuscitation and restoration of circulatory volume 2. Restore total water deficit - 100ml/kg 3. Restore total sodium deficit 7-10mmol/kg 4. Restore total potassium deficit 3-5mmol/kg Shock SBP <90mmHg, HR >100bpm, CRT >2 secs Management: 0.9% Saline aliquots 10mls/kg to max of 30mls/kg or 500-1000ml aliquots Not Shocked (SBP >100mmHg) >70kg Fluid Rate (mls/h) Time (h) 0.9% Sodium chloride 1L 1000 1 0.9% Sodium chloride 1L With potassium chloride* 500 2 0.9% Sodium chloride 1L With potassium chloride* 500 2 0.9% Sodium chloride 1L With potassium chloride* 250 4 0.9% Sodium chloride 1L With potassium chloride* 250 4 0.9% Sodium chloride 1L With potassium chloride* 250 4 0.9% Sodium chloride 1L With potassium chloride* 125 8 Total 7 Litres 25 hours Potassium level (mmol/l) Replacement/litre fluid >5.5 Nil 3.5-5.5 40mmol/L <3.5 60-80mmol/L Seek advice from specialist Assess response to treatment targets 1. CRT <2secs 2. SBP >100mmHg (MAP >70) and HR <100bpm 3. Urine output 0.5ml/kg If poor response to treatment Give fluid boluses of 0.9% Saline aliquots 10mls/kg to max of 30mls/kg or 500-1000ml aliquots INTRAVENOUS INSULIN Aim/Function: 1. Resolution of ketosis 2. Correction of acidosis 3. Resolution of hyperglycaemia if present Fixed dose insulin 0.1unit/kg/hr (round up to the nearest whole number) until resolution of DKA. When CBG <12.0mmol/L Add in 5% Glucose 125mls/hr to enable fixed dose insulin to be continued. When CBG <8.0mmol/L Add in 10% Glucose 125mls/hr to enable fixed dose insulin to be continued. Resolution of DKA: Ketones<0.3mmol/L ph>7.3 Venous bicarbonate>18mmol/l CONTINUE THE 0.9% SALINE WITH THE GLUCOSE Assess response to treatment targets 1. Fall in ketones by 0.5-1.0mmol/hr 2. Rise in bicarbonate by 2.0-3.0mmol/hr 3. Fall in CBG by 3.0-5.0mmol/hr If poor response to treatment Increase insulin by 1.0unit/hr. If after 2 consecutive hours double the fixed dose to 0.2units/kg/hr CRT capillary refill time SBP systolic blood pressure MAP mean arterial pressure CBG = capillary blood glucose
HbA 1c HbA 1c tells you where you have arrived, but does not tell you how you got there. Capillary Blood Glucose (CBG) monitoring tells you the route you have taken. The medication used is the mode of transport.
Daredevil (DD) Double Digits In hospital glucose concentrations in double digits is not good for your patients 6.0 mmol/l In hospital glucose concentrations less than 6 puts your patient's at risk of falling down a slippery slope.