Anaesthesia for diabetic patients : an update

Dr Liwei RenAnaesthetic Registrar Concord HopsitalMay 2013

In this topic – patients with type 2 diabetes (T2DM) for elective operation

Hypoglycaemic agents

Perioperative blood glucose management

Intra operative medications affecting BSL

Diagnosis of DMCriteria Fasting plasma venous glucose (mmol/litre). Glucose load is 75g orally

Diabetes mellitus -    fasting glucose >7.0                                                         2 hour post glucose load >11.1

Impaired glucose tolerance – fasting glucose >7.0                 2 hour post glucose load between 7.8 and 11.1

Impaired fasting glucose – between 6.1 and 7.0 

T2DM: Pathophysiology

relative deficiency of insulin

insulin resistance abnormal hepatic

glucose production progressive

worsening of b-cell function

Current drugs available for the treatment of diabetes mellitus New agents-GLP-1 receptor agonists-DPP-4 inhibitors-Thiazolidinediones (glitazones) -Insulin analogues, basal, and short-acting-Meglitimides-a-Glucosidase inhibitors-Synthetic amylin analogue-SGLT2 inhibitor

Current proven agents—primary treatment-Biguanides-Sulphonylureas

GLP-1 receptor agonists

Exenatide (Byetta) and Liraglutide (Victoza)

MOA-gut-derived peptides secreted rapidly in response to meals-stimulates insulin production and decreases glucagon secretion-slows gastric emptying and suppresses appetite-may also reduce b-cell apoptosis and promote b-cell proliferation

PK: inactivated by DPP-4 enzyme

-synthetic analogues, exenatide and liraglutide are resistant to breakdown by DPP-4 enzyme

SE: nausea, vomiting and diarrhoea occur particularly when starting therapy

withhold preop when fasted

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DPP-4 inhibitors

sitagliptin, saxagliptin and vildagliptin as sole agents and also combined with metformin

MOA: prevent the inactivation of GLP-1 and prolong the activity of the endogenous hormone

PK: oral preparations available, once daily dose

Advantage - a low risk of hypoglycaemia - do not reduce appetite or cause weight loss Adverse events such as increased blood pressure, neurogenic

inflammation, and immunological reactions Withhold pre-op

Thiazolidinediones TZDs (glitazones) ↑Peripheral action of insulin

↓Liver gluconeogenesis

Watch for LFTs

rosiglitazone and adverse cardiac outcomes is still debated by some authorities

Meglitinides

glinides, repaglinide and nateglinide

MOA- stimulate rapid insulin production

PK -faster onset and shorter duration of action than the

sulphonylureas -metabolized and excreted by the liver -can be used in patients with impaired renal function

PD reduce both post-prandial blood glucose and HbA1c

Glucosidase inhibitors: Acarbose inhibits CHO breakdown in gut ‐ ↓Post‐prandial

hyperglycaemia

a reduction in cardiovascular events and a favourable effect on lipid metabolism

watch for LFTs

omit when fasted

Synthetic amylin analogues

Pramlintide

MOA - suppresses glucagon secretion - delays gastric emptying - acts centrally to reduce hunger

Side-effect - nausea is common - hypoglycaemia can occur particularly in the first 4 weeks of

treatment

Sodium-glucoseco-transporter 2 (SGLT2) inhibitors dapagliflozin

MOA inhibits SGLT2 to decrease renal glucose reabsorption and

promotes urinary glucose excretion

Insufficient data at present

Bailey CJ 2010 : RCT showed with no increased risk in hypoglycaemia

Addition of dapagliflozin to metformin provided a new therapeutic option

Biguanides (Metformin/Diabex)

Commonest, first line for the obese ↑Peripheral glucose use

↓Liver GNG

Less likely to cause hypoglycaemia

Metformin does not worsen renal function

Reduce dose with renal impairment due to renal excretion Metabolic acidosis more likely in elderly with associated dehydration and

with higher doses

Metformin

No evidence that metformin is associated with an increased risk of perioperative lactic acidosis (level of evidence [LoE] category1)

Salpeter SR MAIN RESULTS: Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group. Using Poisson statistics the upper limit for the true incidence of lactic acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies.

Metformin- when to stop

If no contra-indications exist, Metformin should be continued up to and including the night before surgery

Discontinue 24 to 48 hours before surgery in the following situations:

- renal dysfunction - surgery involves a major cardiovascular instability - intravenous contrast media

Metformin- when to resume

Should be replaced by an insulin-glucose infusion for the first 24hrs following major surgery before resume

Ensure that the serum creatinine level has not increased significantly

Suphonylureas

E.g. Gliclazide/ Diamicron

K+‐ATP channel blockade (? Prevents ischemic preconditioning)

↑Insulin secretion in response to glucose

↑Peripheral sensitivity to insulin

SE hypoglycaemia

Insulin

Increasingly, insulin is no longer seen as a ‘last resort’ after long-term oral agent combinations have failed, but as a therapeutic tool for earlier use.

Insulin

Short-acting - Human (Novorapid) onset: 25-30 mins, peak: 1-3 h, last: 3-5h- Regular insulin (actrapid) onset: 30-60 mins, peak: 2-4 h, last: 5-8h

Intermediate-acting insulin includes Isophane (Protaphane) onset: 1-2 h, peak: 4‐12 h, last: 16-24h

long-acting insulin includes Glargine (Lantus) onset: 2‐4 hours, NO peak, last: 24h

Insulin

basal-bolus : insulin therapy should address both basal and post-prandial insulin requirements

basal insulin to suppress glucose production between meals and overnight

- daily dose

bolus insulin to limit postprandial hyperglycaemia

- dose before meals

Long acting (basal) insulin

Insulin glargine provides a constant release of insulin from the injection site over 24 h without the risk of hypoglycaemia

For patients not requiring an insulin glucose infusion, there is debate about whether the dose of long acting insulin analogue should be reduced by one third or maintained at the usual level.

Long acting (basal) insulin

As a rough guide, if the patient reports that the blood glucose falls by more than 2 mmol/L overnight it would be prudent to reduce the basal insulin. If the blood glucose remains stable overnight the normal basal insulin dose should be maintained.

long-acting analogues

Consider continuation of long-acting analogues (Glargine/Lantus®), alongside the Insulin glucose

infusion during the peri-operative period.

Long-acting insulin

Provides good glycaemic control between meals Allows a relatively constant basal insulin supply for more

than 24 h

Continuation of the basal insulin throughout the perioperative period is logical and has been adopted in some centres. Advantage is no time is lost in re-establishing basal insulin once the insulin dextrose is discontinued

Pre-operative assessment Diabetes Type Duration Treatment Cardiovascular disease -Coronary artery disease-Peripheral vascular disease-Hypertension-Cerebrovascular disease

Renal disease Peripheral neuropathy and possibly autonomic neuropathy Metabolic control, HbA1C Airway, cervical spine, stiff joint syndrome Gastroparesis, reflux symptoms Drugs and allergies

Perioperative Management

Perioperative concerns - Surgical Stress Response - ↑GH, Cortisol, Catecholamines > Anti‐insulin

- discontinuation of hypoglycemic medications and insulin - Hyperglycaemic effects

Interruption of food intake

Altered consciousness (unable to respond to hypoglycaemia

Problems with peri operative hyperglycaemia “Stress response” to surgery

↑Stress hormones secretion in presence of relative insulin deficiency

Deficiency is ↓secretion and ↑resistance

Dehydration (Glycosuria causing osmotic diuresis) and electrolytes derangement

Acidaemia (Lactic mainly, Ketoacids)

Poor healing, Infections, ↑Mortality

Problems with hyperglycaemia

impairs reactive endothelial nitric oxide generation

increases expression of leukocyte and endothelial adhesion molecules

decreases complement function

impairs neutrophil chemotaxis and phagocytosis enhances the synthesis of inflammatory cytokines

Problems with peri operative hyperglycaemia Improved glycaemic control perioperatively improves

healing

a retrospective survey (by Frisch A etc. ) found that peri operative hyperglycaemia was associated with increased length of hospital stay, morbidity, and mortality after non-cardiac general surgery in diabetic and non-diabetic patients

Infections

Perform invasive procedures with full asepsis

Hypoglycemia

Main concern-irreversible brain damage

Intraoperative hypoglycemia is hard to detect clinically

-Sympathetic responses are ablated by anaesthesia

Perioperative blood sugar level (BSL) target

Controversial

Aim for BSL between 6-10 mmol/L, but 4-12 mmol/L is acceptable

Avoid wide swings

Perioperative target for therapy – Australian Diabetes Society 2012 Postpone elective surgery if possible if glycaemic control is poor

(HbA1c ≥ 9%)

BSL should be kept between 5 – 10mmol/l during the peri-operative period

For critically ill patients who require admission to the intensive care

unit post-operatively, a “tighter” BSL target (eg 4.4-6.1 mmol/L) may not convey any greater benefit

Hypoglycaemia must be avoided

HbA1c

Pre-operative glycaemic control also influences the risk of post-operative wound infection, with a study (Dronge et al, 2006 ) suggesting a HbA1c ≥ 7% more than doubles this risk

HbA1c level

Average blood glucose over the past 2 to 3 months

There is evidence that good control pre-operatively, as measured by the HbA1c level is associated with improved outcomes after a range of non-cardiac surgical procedures

Estimated average glucose levels (eAG) eAG = (1.6 x HbA1c) – 2.6 mmol/L

HbA1c level

An elevated pre-operative HbA1c is associated with poorer outcomes whether diabetes has been diagnosed or not.

There may be a role for routine measurement of HbA1c at pre-operative assessment in undiagnosed patients with risk factors for diabetes.

Management (assumes that the HbA1C is ≤ 8-10% ) In general: Type 2

Withhold morning OHG

Withhold or halve normal morning insulin with 5% dextrose (40‐80ml/h) BSL q1-2h – titrating 5% dextrose according to BSL

GENERAL PRINCIPLES

Diabetes should be well controlled prior to elective surgery. Avoid insulin deficiency, and anticipate increased insulin requirements. The patient’s diabetes care provider should be involved in the management of their

patients’ diabetes peri-operatively. Patients must be given clear written instructions concerning the management of their

diabetes both pre- and post-operatively (including medication adjustments) prior to surgery.

Patients must not drive themselves to the hospital on the day of the procedure.

Patients with diabetes should be on the morning list, preferably first on the list. These guidelines may need to be individually modified depending on the patient’s

circumstances. It is important that advice concerning diabetes management be provided by someone

who is familiar

Anaesthetic Management- Regional Anaesthesiabenefits modulates stress

hormone secretion, may improve perioperative BSL control

allows early resumption of oral intake

risks profound hypotension

with autonomic neuropathy

increased risk of infection / vascular damage

confusion between neuropathy and anaesthetic complication

General Anaesthesia

high dose Benzos: ↓Cortisol secretion, ↓SNS, ↑GH

high dose Opioids: Blocks SNS, ↓Catabolic responses

volatiles: Inhibits insulin response to glucose in vitro (dose‐related)

Dexamethasone yes or no

Intra-operative monitoring anddocumentation Frequency of BSL monitoring should be determined by the clinical

circumstances

NICE guidelines recommend that the blood glucose be monitored every 30 minutes during caesarean section

No recommendations for other procedures but hourly blood glucose measurement should suffice if the blood glucose is stable and in the target range.

Intraoperative BSL management

Consider changing to a insulin glucose infusion if the blood glucose cannot be kept below 12 mmol/L

Postoperative care goal

Adequate analgesia

Treatment of postoperative nausea and vomiting

Return to the patient’s normal diabetic regimen as soon as possible

Oral agents should wait until reliable diet

Summary

In order to keep blood glucose levels within the target range, diabetes medications often need to be altered immediately before and following surgical procedures

Very important to monitor and manage peri-operative BSL to minimize hyperglycaemia and hypoglycaemia (especially under GA)

Thank you!

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