Peri-operative management of diabetes mellitus · Peri-operative management of diabetes mellitus ... DM or glucose > 11mM Iv insulin started at 5 units/hr, ... Peri-operative management

Peri-operative

management of

diabetes mellitus

Dr.Martin Whyte

Consultant Diabetes & Endocrinology

Peri-operative management of

diabetes mellitus

Why is peri-operative control important?

Metabolic response to surgery / infection risk

Evidence to support peri-operative glycaemic control

Pre-operative evaluation

Glycaemic target & choice of medication / regime

What to do on the day of surgery itself

Why is peri-operative glycaemic

control important?

2.5 million people with diabetes in UK

25% of diabetic patients will require

surgery at some point

12 to 25% of hospitalised patients have

DM

Hyperglycemia: an independent marker of

in-hospital mortality in patients with

undiagnosed diabetes

Umpierrez et al. JCEM 2002; 87; 978-982

The Relation Between Hyperglycemia and

Outcomes in 2,471 Patients Admitted to the

Hospital With Community-Acquired Pneumonia

≤6.1 6.1–11.0 11.1–13.9 ≥ 14

McAllister et al. Diabetes Care 2005; 28: 810-815

Glycaemic control before surgery

Non-cardiac surgery 1991 – 2001

Candidate cases were 904 deaths

occuring within 30-days of surgery

1247 case controls matched to age,

gender, year of op, type of surgery

Comparison of pre-operative glucose

values

Noordzij et al. Eur J Endo 2007;156:137-142

Increased preoperative glucose levels

are associated with peri-operative

mortality

Noordzij et al. Eur J Endo 2007;156:137-142

Peri-operative management of

diabetes mellitus

Why is peri-operative control important?

Metabolic response to surgery / infection risk

Evidence to support peri-operative glycaemic control

Pre-operative evaluation

Glycaemic target & choice of medication / regime

What to do on the day of surgery itself

Metabolic response to surgery

Stress Response

(TNFα, IL-1, IL-2,IL-6, IL-8)

Adrenal medulla Central Nervous

System

Adrenaline Hypothalamus

& noradrenaline

Adrenal cortex

Cortisol

Liver

Skeletal

muscle

Adipose

tissue

Glycogenolysis

Gluconeogenesis

Insulin

resistance

NFκB binding at the

nuclear level

H

Y

P

E

R

G

L

Y

C

A

E

M

I

A

Lipolysis

Proteolysis

Glycerol

Alanine

Glutamine

BS > 11.1 mmol/L

Renal threshold for glycosuria (normal GFR)

Impaired WBC function

Chemotaxsis

Phagocytosis

Impaired wound healing

Peri-operative management of

diabetes mellitus

Why is peri-operative control important?

Metabolic response to surgery / infection risk

Evidence to support peri-operative glycaemic control

Pre-operative evaluation

Glycaemic target & choice of medication / regime

What to do on the day of surgery itself

DIGAMI 620 pts. AMI. DM or glucose > 11mM

Iv insulin started at 5 units/hr, target gluc 7-10.9mM

At 24 hrs insulin switched to sc for 3/12

No in-hospital mortality benefit

Increased LoS by 1.8 days

0.5% reduction HbA1c at 3/12

At 1 year: 72% Rx group and 49% controls on insulin

1 year mortality: ARR 7.5% NNT 13

3.5 year mortality: ARR 11% NNT 9

Evidence to support inpatient

glucose control?

Malmberg et al. J Am Coll Cardiol 1995; 26: 56-65

Control Group

N=968

1987-1991

s/c insulin 4 hrly

Goal 11.1mmol/L

Standard Deviation 36

All Mean BG‟s

<11.1mM 47%

Study Group

N=1499

1991-1997

IV Insulin

Goal 8.3-11.1 mmol/l

Standard Deviation 26

All Mean BG‟s

<11.1mM 84%

Continuous intravenous insulin infusion reduces

the incidence of deep sternal wound infection in

diabetic patients after cardiac surgical procedures

Furnary et al. Ann Thoracic Surg 1999; 67: 352-360

1548 ICU patients (63% cardiovascular surgery)

If BS > 6.1 mM: Rx with IV insulin gtt & TPN +/- tube feeds

Start IV insulin @ 2-4 U/h, titrated to BS 4.4-6.1 mM

Mean insulin dose: Rx group 3.0 U/h Control group 1.4 U/h

Once out of ICU relaxed treatment goal to < 11.1 mM

Mortality in ICU: ARR 3.4% NNT 29

Mortality in-hospital: ARR 3.7% NNT 27

Greatest reduction in mortality was sepsis-related.

Insulin Rx reduced: bacteremia, ARF needing HD, need for PRBC, critical illness polyneuropathy, duration of ventilation and length of stay in ICU

Intensive insulin therapy in critically ill

patients

Van den Berghe et al. NEJM 2001; 345: 1359 - 1367

Hypoglycaemia rate in ICU studies

Griesdale et al. CMAJ 2009; 180(8): 821-827

Griesdale et al. CMAJ 2009; 180(8): 821-827

Association between lowest recorded blood glucose during hospitalization and incidence of death within 2 years.

Svensson A et al. Eur Heart J 2005;26:1255-1261

Mean glucose & in-hospital

mortality in 16,871 patients AMI

Kosiborod et al. Circulation 2008; 117: 1018 - 1027

Peri-operative management of

diabetes mellitus

Why is peri-operative control important?

Metabolic response to surgery / infection risk

Evidence to support peri-operative glycaemic control

Pre-operative evaluation

Glycaemic target & choice of medication / regime

What to do on the day of surgery itself

Pre-operative evaluation

Cardiopulmonary risk

Greater risk of CAD and silent ischaemia

Long-term complications of DM

Baseline glycaemic control – HbA1c

If >9% liase with diabetes team

If >12% consider delaying surgery to achieve better control

Medication

Type of surgery

Peri-operative Beta-blockade Diabetic Postoperative Mortality and Morbidity

(DIPOM) trial Diabetics >39 years old.

Non-cardiac surgery.

Naive to beta-blockers

Metoprolol started the night before surgery (100mg) and continued for ~ five days

Outcomes: all-cause mortality, acute MI, USAP, and CHF, measured for a median of 18 months

2066 patients were eligible. Only 921 were randomized (45% of eligible patients)

99 events Metoprolol group vs 93 placebo

Angeli et al. Ther Adv Cardiovasc Dis 2010; 4(2): 109 - 118

Revascularisation pre-op?

Death

or

non-fatal MI

Poldermanns et al. J Am Coll Cardiol 2007; 49: 1763 - 1769

Peri-operative management of

diabetes mellitus

Why is peri-operative control important?

Metabolic response to surgery / infection risk

Evidence to support peri-operative glycaemic control

Pre-operative evaluation

Glycaemic target & choice of medication / regime

What to do on the day of surgery itself

Start oral medication?

No

Contraindications or SEs of oral meds

Little flexibility or opportunity for titration in a setting where acute changes demand these characteristics.

Therefore use insulin

Randomised study of Basal Bolus insulin therapy

in the Inpatient Management of Patients with Type

2 Diabetes undergoing General Surgery

(RABBIT2)

Patients with DM for ≥3/12. Admission glucose 140-400mg/dL. Insulin ≤0.4U/kg

Elective or emergency surgery. Not expected to need ICU

Glargine + glulisine (n=104) vs PRN Actrapid (n=107; QDS max)

Target fasting 100-140mg/dL

OHAs discontinued. Basal bolus 0.5U/kg (50% as basal, 50% as bolus)

Outcomes: daily blood glucose (BG); wound infection, pneumonia, bacteraemia, and respiratory and acute renal failure.

On admission 17.1% diet, 63% oral, 9.5% oral + insulin, 10.4% insulin alone

HbA1c 7.72 ± 2.2%

Umpierrez et al. Diabetes Care 2011; 34(2): 256-261

PRN Actrapid

Basal bolus

<3.8mmol/L

<2.2mmol/L

<3.3mmol/L

Comparison of in-patient regimens with

Detemir plus Aspart versus NPH plus

regular in Medical Patients with Type 2

diabetes multicentre trial

130 nonsurgical patients BG 7.8 to 22.2 mmol/L to detemir OD plus aspart before meals (n = 67)

neutral protamine Hagedorn (NPH) and regular insulin twice daily (n = 63).

Insulin dose started at 0.4 U/kg/d for BG between 7.8 and 11.1 mmol/L or 0.5 U/kg/d for BG 11.1-22.2 mmol/L.

Study outcomes: differences in mean daily BG levels

frequency of hypoglycemic events

Umpierrez et al. JCEM 2009; 94: 564 - 569

Results Twice daily NPH + Actrapid

Detemir + Aspart

Detemir + Aspart

Twice daily NPH + Actrapid

Starting Insulin Regimen

TDD = 0.3-0.5 U/kg

“2/3, 1/3” Regimens 2/3 of TDD before Breakfast, 1/3 before Dinner

Pre-mix (30/70)

MDI Regimens basal 50%, bolus 50% (divided by 3)

How to calculate correctional doses

Correction dose to lower blood glucose = 100/TDD

If taking 20 units per day then 100/20 = 5mM

Hence 1 unit will lower by 5mmol/L.

If taking 50 units per day then 100/50 = 2mM

Hence 1 unit will lower by 2mmol/L

Guideline for Insulin Adjustments

1. Adjust the insulin that accounts for the high or low

reading.

2. Always compare an abnormal BS reading with the one

previous.

3. If insulin dose is:

• Less than 8U, adjust by 1U

• 8-20U, adjust by 2U

• > 20 U, adjust by 10% (increase), 20% (decrease)

4. Don‟t forget to compensate for a successful

adjustment

Consensus Recommendations for Target

Inpatient Blood Glucose Concentrations

Patient population Blood glucose target Rationale

General medical /

surgical*

Fasting 5 - 7

Random < 11.1 (?<10)

↓ mortality, LoS,

↓ infection rates

Cardiac surgery* < 8.3 ↓mortality

↓Sternal wound infection

Critically ill† < 8.3 ↓mortality, morbidity, LoS

Acute neurologic

disorders ‡

4.4 – 7.8 No data!!

*ADA

† Society of Critical Care Medicine

‡ American Heart Association / American Stroke Association

Peri-operative management of

diabetes mellitus

Why is peri-operative control important?

Metabolic response to surgery / infection risk

Evidence to support peri-operative glycaemic control

Pre-operative evaluation

Glycaemic target & choice of medication / regime

What to do on the day of surgery itself

Non-insulin antidiabetic medications

Short acting eg glicazide, replaginide Omit on day of surgery

Long acting eg glicazide MR, glipizide Omit on day prior to surgery

Thiazolidinediones eg rosiglitazone, pioglitazone Omit on day of surgery

Metformin Stop 48 hours before surgery

Acarbose Omit day of surgery

Gliptins eg sitagliptin Omit day of surgery

Incretin mimetics eg exenatide Omit on day of surgery

Metformin

Contraindications eGFR < 30mls/min

CHF symptomatic (> NYHA class III, E.F. < 35-40%)

Liver failure

Alcoholism

Hypoxic respiratory condition

Active moderate to severe infection

Radio-contrast or Surgery with GA

Hold metformin for 24 - 48h

Restart after documented preservation of renal

function

Pre-operative insulin administration

Type of insulin Morning list Afternoon list

Twice daily Mix

eg Novomix

Omit morning

S/scale 0800

50% in morning

S/scale 1200

Twice daily intermed.

acting eg insulatard

Omit morning

S/scale 0800

50% in morning

S/scale at 1200

Once day long acting

in morning eg

glargine

75% day prior

Omit morning

S/scale 0800

Omit morning

S/scale at 1200

Once a day long

acting in evening

75% day prior

S/scale 0800

75% day prior

S/scale 1200

Short acting eg

Novorapid, Actrapid

Omit morning 75% morning

Omit lunch

Management of patients on insulin

(Type 1 and Type 2)

For morning surgery Ensure that no sc rapid acting or pre-mixed insulin given on the day

of surgery The last dose of either type of insulin should be on the previous evening

Check the blood glucose

Commence sliding scale

Continue to check the blood glucose hourly pre, intra and post-operatively

Post-operatively Change to sc insulin post-operatively when eating normally

Important to continue sliding scale for 60 mins after first sc insulin injection

Day-case surgery Aim for “first on list”

For those on multiple injection regimen, continue usual basal (long acting) insulin on evening prior to procedure

For patients on bd insulin, continue the usual evening insulin prior to the procedure

Fast from midnight and omit the morning insulin

Check BM before and after the procedure

Resume the usual insulin and diet after the procedure. If a BD insulin regimen is restarted at lunchtime give half of normal „breakfast‟

insulin dose with lunch after procedure

The above applies if rapid recovery is expected i.e. the patient is expected to be eating within 2 hours of the procedure

If the patient is unable to tolerate diet or the blood glucose is >14 mmol/L, then a sliding scale may be required

Take-home messages - 1

Hyperglycaemia is frequent in hospitalised

patients with and without a history of diabetes

Hyperglycaemia (?hypoglycaemia) is a marker

of poor outcome in critically and non-critically ill

patients

Improvement in clinical outcome has been

shown by improved glycaemic control in a

variety of inpatient settings.

Patients with T1DM & insulin-treated T2DM should continue usual therapy.

Avoid using purely PRN Actrapid

No data to support benefit of insulin analogues (esp basal) in hospital.

Take-home messages - 2