British Journal of Anaesthesia 85 (1): 8090 (2000)

Anaesthetic management of patients with diabetes mellitus

G. R. McAnulty1, H. J. Robertshaw2 and G. M. Hall1*
1

Department of Anaesthesia and Intensive Care Medicine, St George's Hospital Medical School, London
SW17 0RE, UK. 2Department of Anaesthesia, Imperial College of Science, Technology and Medicine,
Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
*Corresponding author
Br J Anaesth 2000; 85: 8090
Keywords: complications, diabetes; blood, glucose; hormones, insulin; metabolism,
hypoglycaemia

The prevalence of diabetes mellitus in both adults and

children has been steadily rising throughout the world for
the past 2030 yr.29 55 97 Recent changes in diagnostic
criteria, if widely adopted, will probably also lead to more
patients being classied as having diabetes.16 Inevitably,
diabetic patients presenting for incidental surgery, or
surgery related to their disease, will place an increasing
burden on anaesthetic services. Conict will occur between
an economic need to minimize hospital stay and traditional
approaches to managing perioperative diabetic patients that
rely on a period of inpatient preoperative `stabilization'.
Better glycaemic control in diabetic patients undergoing
major surgery has been shown to improve perioperative
mortality and morbidity.44 90 Simple avoidance of hypoglycaemia and gross hyperglycaemia are no longer adequate in
the light of this knowledge. While there can be little
argument about the management of diabetic patients
undergoing major procedures, their management for minor
surgery is an increasing dilemma. Under what circumstances are day-case anaesthesia and surgery appropriate?
Does admission on the day of surgery add to the risk for the
diabetic patient? What investigations, if any, are needed to
assess the cardiovascular system of an asymptomatic
diabetic who presents for major surgery? Unfortunately,
there are few data to provide answers to these questions. An
understanding of the pathophysiology of diabetes and of the
importance of recent research should improve the perioperative care of diabetic surgical patients. This review will
discuss some recent developments in the eld. It will not
provide `recipes' or algorithms for management. These can
be found in any of the standard texts.

Revised diagnostic criteria for diabetes

mellitus
Recently, both the American Diabetes Association (ADA)
and the World Health Organization (WHO) published

recommendations for new diagnostic criteria for diabetes

mellitus.1 106 Both bodies advise a reduction in the threshold
limit for fasting plasma glucose concentrations and reafrm
a more aetiologically based nomenclature. The terms type 1
(pancreatic B-cell destruction) and type 2 (defective insulin
secretion and, usually, insulin resistance) diabetes are
recommended to replace completely the frequently misleading terms `insulin-dependent' and `non-insulin-dependent' diabetes. The ADA has specied that the diagnosis of
diabetes mellitus should be made if a `casual' (random)
plasma glucose value in an asymptomatic individual is
>11.1 mmol litre1. If a fasting plasma glucose is >7.0 mmol
litre1 (6.1 mmol litre1 blood glucose) in an asymptomatic
individual, the test should be repeated on a different day and
a diagnosis made if the value remains above this limit. The
ADA denes fasting plasma glucose concentrations between 6.1 and 7.0 mmol litre1 (5.66.1 mmol litre1 blood
glucose) as representing `impaired fasting glycaemia'. The
WHO also recommends that a diagnosis of diabetes mellitus
be made if a random plasma glucose concentration is >11.1
mmol litre1 (venous whole blood >10.0 mmol litre1). It
can also be diagnosed with a fasting plasma glucose
concentration of >7.0 mmol litre1 and a second similar
test or an oral glucose tolerance test producing a result in the
diabetic range.
The change in the fasting plasma glucose concentrations used to dene diabetes and the role of a standard
oral glucose tolerance test may make it difcult to
compare epidemiological studies using these new criteria
with those using previous ones. Inevitably, some individuals will be diagnosed as having diabetes using
criteria based solely on (lower) fasting plasma glucose
concentrations who would not have been so diagnosed
under the earlier denitions. There will be others who
would have fullled the denition using an oral glucose
tolerance test but who will have acceptable fasting
values. Thus it is likely that the new denitions will

The Board of Management and Trustees of the British Journal of Anaesthesia 2000

Diabetes mellitus

dene as diabetic a group of glucose intolerant individuals.52

In addition to the two common types of diabetes, a
number of causes of glucose intolerance can be dened
according to a specic causal or pathological process.
Gestational diabetes is glucose intolerance which has its
onset in, or is rst diagnosed during, pregnancy. The
severity varies and the denition applies whether or not
insulin is administered in treatment. Women with diabetes
diagnosed before pregnancy are dened as having `diabetes
mellitus and pregnancy', not gestational diabetes.1 The
neonatal outcome of type 1 diabetic women who become
pregnant is poor. Their infants are approximately ve times
more likely to be stillborn and 10 times more likely to have
congenital malformations than those born to non-diabetic
mothers.10 Management in a specialist centre may improve
the incidence of perinatal mortality.34 Abnormally increased membrane transport of glucose, even in mothers
whose diabetes is well controlled, may explain the continuing high rates of congenital malformations (particularly
macrosomia) despite improved treatment.48 Increasing the
frequency of insulin administration from two to four times
daily during pregnancy can lead to better maternal
glycaemic control with a lower incidence of neonatal
hypoglycaemia and hyperbilirubinaemia without increasing
the risk of maternal hypoglycaemia.73
There is a number of rare genetic causes of glucose
intolerance. Among these are defects of B-cell function
(formerly called maturity-onset diabetes of the young, or
MODY) and defects in insulin action (formerly called type
A insulin resistance). Diffuse diseases of the exocrine
pancreas (such as pancreatitis), specic viral infections
which destroy pancreatic B cells (rubella, Coxsackie B,
cytomegalovirus, mumps and others) and immune-mediated
processes (insulin autoantibodies or insulin receptor antibodies) can also lead to a `diabetic state'.1 Endocrinopathies
associated with excess secretion of counter-regulatory
hormones (such as growth hormone, cortisol, glucagon
and epinephrine) can lead to hyperglycaemia.
A number of drugs can induce glucose intolerance either
by inhibiting the secretion of insulin or by interfering with
the peripheral action of insulin.1 In anaesthesia, glucocorticoids and adrenergic agonists are most frequently implicated. The new oral corticosteroid, deazacort, may be less
`diabetogenic' than prednisolone or betamethasone.2
`Metabolic syndrome' (also called syndrome X or insulin
resistance syndrome) is a non-causally linked cluster of
symptoms which carry a high risk of macrovascular disease.
The cluster includes impaired glucose tolerance or diabetes,
insulin resistance, raised arterial pressure, raised plasma
triglycerides, central obesity and microalbuminuria.1

processes are inhibited by minimal levels of insulin

secretion and are rare in type 2 diabetics unless there is an
additional stress such as sepsis or dehydration.122
Obviously, both groups are subject to the effects of
hyperglycaemia.
Diabetics are at increased risk of myocardial ischaemia,
cerebrovascular infarction and renal ischaemia because of
their increased incidence of coronary artery disease,94
arterial atheroma51 and renal parenchymal disease.14
Increased mortality is found in all diabetics undergoing
surgery44 90 and type 1 diabetics are particularly at risk of
post-operative complications.111 Increased wound complications are associated with diabetes24 64 72 126 and
anastomotic healing is severely impaired when glycaemic
control is poor.118
The `stress response' to surgery is associated with
hyperglycaemia in non-diabetic patients as a result of
increased secretion of catabolic hormones in the presence of
a relative insulin deciency. This deciency arises from a
combination of reduced insulin secretion41 and insulin
resistance.109 Insulin resistance may result, in part, from the
increase in secretion of catecholamines, cortisol and growth
hormone42 and involves an alteration of post-receptor
binding of insulin and subsequent reduction of transmembrane glucose transport.79 Some, at least, of the
metabolic effects of the suppression of insulin secretion
are reversed by intraoperative insulin infusion37 and both
oral and i.v. perioperative administration of glucose
enhance postoperative glucose utilization rates.56 62 80

Adverse effects of hyperglycaemia

The consequences of a reduction in, or complete lack of,
insulin-mediated metabolic processes can be classied
according to chronicity and to histopathological effects.
Acute consequences of untreated, or inadequately treated,
diabetes mellitus include dehydration (resulting from the
osmotic diuretic effect of glycosuria), acidaemia (because
of accumulation of lactic and/or ketoacids), fatigue, weight
loss and muscle wasting (because of lipolysis and
proteolysis in absolute insulin deciency). Ketoacidosis is
rare in type 2 diabetics but is frequently a presenting
symptom of type 1 disease. It is a medical emergency that
still carries a considerable mortality rate of up to 15%.4 49
The mortality of hyperosmolar non-ketotic hyperglycaemic
coma in type 2 diabetics may be even greater,63 probably
reecting a more elderly population with a higher incidence
of co-existing disease.
Ketoacidosis is treated by rehydration and insulin
infusion with frequent measurements of serum electrolytes
and acidbase status. Sequential estimations of blood
b-hydroxybutyrate concentrations and concomitant continuation of intensive insulin therapy may expedite treatment.124 Non-ketotic hyperglycaemic coma is frequently
precipitated by infection and is commonly associated with

Pathophysiology
Type 1 diabetics completely lack insulin secretion, making
them prone to lipolysis, proteolysis and ketogenesis. These
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McAnulty et al.

multi-organ system dysfunction. Blood glucose concentrations may be extremely high.33

Chronic effects of diabetes can be divided into microvascular (including proliferative retinopathy and diabetic
nephropathy), neuropathic (autonomic and peripheral
neuropathies) and macrovascular complications (atherosclerotic disease). The incidence of microvascular and
neuropathic complications in types 1 and 2 diabetics is
similar when adjusted for duration of disease and quality of
glycaemic control. The cumulative lifetime incidence of
proliferative retinopathy, proteinuria and distal neuropathy
is roughly 50% for both type 1 and type 2 diabetics. This
implies that the primary cause of these complications is
hyperglycaemia itself, as the underlying metabolic pathology is different for type 1 and type 2 disease.31
Macrovascular complications (as measured by rates of
coronary artery, cerebrovascular and peripheral vascular
disease) are also similar for type 1 and 2 diabetics
(cardiovascular mortality is 3054% for type 1 and 38
41% for type 2 diabetes).31 In type 2 patients, at least,
abnormally high concentrations of plasminogen activator
inhibitor-1 (PAI-1) and, therefore, impaired brinolysis,
have been implicated in the accelerated rates of development of atherosclerotic disease.83
Improved glycaemic control has a benecial effect on
microvascular and neuropathic complications in type 2
diabetes.114 Although there is probably no adverse effect,83
improvement in glycaemic control alone appears not to
improve the incidence of macrovascular disease in these
patients.114 However, tight control of blood pressure (with
an angiotensin-converting enzyme inhibitor or a b-blocker)
in patients with type 2 diabetes and hypertension reduces the
risk of diabetes-related death, including that secondary to
macrovascular complications, as well as the risk of other
diabetes-related complications and eye disease.115 116

may be frequently too short to avoid periods of hypoinsulinaemia and subsequent risk of lipolysis and proteolysis in
patients with no endogenous insulin secretion.
Insulin is synthesized in the pancreas as part of a longerchain protein called proinsulin. This is cleaved by membrane-bound proteases producing the polypeptides insulin
and C-peptide. These two polypeptides are secreted into the
circulation in equimolar amounts. C-peptide is useful
experimentally in determining native insulin production in
type 2 diabetic subjects receiving insulin. It was once
thought that C-peptide had no physiological role other than
facilitating the folding of the proinsulin molecule. However,
more recent studies point to a possible role for C-peptide in
glucose transport in skeletal muscle, renal tubular function
and in the prevention of autonomic neuropathy.119

Hypoglycaemic therapy
Type 1 diabetics require insulin. Type 2 diabetics may
require insulin but, in many cases, maintain reasonable
glycaemic control with an appropriate diet and often the use
of oral hypoglycaemic drugs.
Therapeutic insulin may be extracted from beef (now
rarely used) or pork pancreas, or synthesized using
recombinant DNA technology from Escherichia coli.6 The
amino acid sequences of insulin differ somewhat between
species; however, modifying porcine insulin can produce
human-sequence insulin. It was hoped that the replacement
of animal- by human-sequence insulins would reduce the
induction of antibodies and therefore insulin resistance, but
clinical trials have been disappointing.66
The three types of insulin preparation are classied
according to their length of action. Soluble insulins have a
rapid onset and short duration of action (depending upon the
route of administration). When injected subcutaneously the
duration of action is from 30 min up to 8 h with a peak at
24 h. Human-sequence soluble insulin has a slightly
shorter onset time and duration of action. Insulin lispro, a
recently introduced recombinant human insulin analogue,
has an even shorter duration of action. Soluble insulin
injected i.v. has a half-life of approximately 5 min.6
Longer-acting insulin preparations are made with suspensions of insulin with either protamine (`isophane insulin') or zinc (`crystalline insulin') salts or both together.
They are often administered in combination with soluble
insulin to obtain rapid onset together with a long duration of
action.6 They are not suitable for i.v. use. Long-acting
insulins may act for up to 36 h for animal-91 and 24 h for
human-sequence preparations.47
There are four groups of oral hypoglycaemic agents: the
sulphonylureas, the biguanides, the (recently developed)
thiazolidinediones and modiers of glucose absorption from
the gut. In the main, sulphonylureas enhance the secretion of
insulin in response to glucose and increase sensitivity to its
peripheral actions. Biguanides (metformin is the only
compound in this group available in the UK) promote

Diabetic therapy
The problems of insulin replacement
Insulin is secreted into the bloodstream from pancreatic
B cells via the portal system so that there is normally a
portalperipheral insulin concentration gradient which cannot be mimicked by subcutaneous or i.v. insulin administration. Additionally, even the most sophisticated articial
insulin delivery systems cannot hope to replicate the
complex local interaction between the B cells and A, D
and PP cells of the islets of Langerhans (which secrete
glucagon, somatostatin and pancreatic polypeptide, respectively) and the effects of the extrapancreatic neurohormonal
system. Insulin secretion in response to varying states of
feeding or starvation changes by 20- to 50-fold and
maintains a basal insulin secretion during the fasting state.
Insulin administered subcutaneously, even if timed optimally, will inevitably have inadequate peak concentrations
for expected postprandial periods, and its duration of action
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Diabetes mellitus

solutions with a concentration of insulin of >400 ng ml1

(~10 U litre1) the effect is minimal.8 However, signicant
amounts of insulin may be adsorbed on to giving sets,
particularly if they have a relatively high surface area,
thereby reducing initial rates of insulin delivery if a highvolume, low-insulin concentration regimen is used.69 More
consistent delivery can be achieved with more concentrated
solutions of lower volume administered from a syringe.92
When normal oral nutrition is not possible, parenteral
administration of carbohydrate is required to safeguard
against inadvertent hypoglycaemia and excessive catabolism. Safety is always a concern when insulin infusions are
administered. Glucoseinsulinpotassium (GIK) systems,
such as the Alberti regimen, are inherently safe because they
provide insulin and glucose in the same solution.107 With
separate glucose and insulin infusions one may be stopped
inadvertently with potentially disastrous consequences.
However, separate infusions were preferred by nursing
staff and resulted in marginally improved perioperative
glycaemic control when compared with a GIK system in one
randomized controlled trial of 58 surgical patients.101 Fifty
per cent glucose solutions containing 0.25 or 0.5 U insulin
ml1 can provide amounts of glucose and insulin equivalent
to the more conventional systems using 10% glucose and
avoid the administration of large volumes of free water.68
However, the hypertonic 50% solution needs to be infused
into a central vein.

glucose utilization and reduce hepatic glucose production.

Thiazolidinediones, which are still under clinical evaluation
(and currently under a cloud because of reported hepatotoxicity), enhance insulin action in the periphery and inhibit
hepatic gluconeogenesis, perhaps via a specic receptor
mechanism. The a-glucosidase inhibitor, acarbose, suppresses the breakdown of complex carbohydrates in the gut
and therefore delays the rise in postprandial blood glucose
concentrations.100
Intensive, effective glycaemic control of type 2 diabetes
results in a reduction of microvascular, but probably not
macrovascular, complications of the disease.31 114 Where
adequate control can be achieved (haemoglobin A1c
concentration 78%31) there is no clear advantage for any
therapeutic agent; oral hypoglycaemics and insulin have
similar effects.76 Metformin may be a better choice in obese
type 2 diabetics. It was associated with a lower incidence of
mortality and diabetes-related morbidity when used as a
rst-line treatment compared with either sulphonylureas or
insulin in the recently-reported UK Prospective Diabetes
Study (UKPDS).113 However, addition of metformin to
patients receiving sulphonylureas in the UKPDS was
associated with a worrying increase in mortality. Despite
concerns about rare but potentially lethal lactic acidosis,
which may be more likely in the elderly,100 in association
with renal failure25 and hepatic failure and after surgery,71
metformin is well tolerated and less likely to cause
hypoglycaemia than sulphonylureas or insulin.28 113
Interest in the potassium channel-blocking effect of
sulphonylureas and, hence, interference with myocardial
ischaemic preconditioning, has increased recently.5
Glimepiride may not block potassium channels,58 but
angioplasty patients receiving sulphonylureas have greater
mortality and morbidity than those given insulin.30 The
general implications of this observation are not clear but,
until data from well-conducted studies are available, it
would seem prudent to convert patients taking sulphonylureas to insulin several days before cardiac or other major
surgery or procedures where myocardial perfusion may be
compromised.

The metabolic challenge of surgery for the

diabetic patient
The immediate perioperative problems facing the diabetic
patient are: (i) surgical induction of the stress response with
catabolic hormone secretion; (ii) interruption of food intake,
which may be prolonged following gastrointestinal procedures; (iii) altered consciousness, which masks the symptoms
of hypoglycaemia and necessitates frequent blood glucose
estimations; and (iv) circulatory disturbances associated
with anaesthesia and surgery, which may alter the absorption of subcutaneous insulin.
Surgery evokes the `stress response', that is, the secretion
of catecholamines, cortisol, growth hormone and, in some
cases, glucagon. These hormones oppose glucose homeostasis, as they have `anti-insulin' and hyperglycaemic
effects. Gluconeogenesis is stimulated and peripheral glucose uptake decreased. Although diabetics need increased
insulin during the perioperative period, requirements for
glucose and insulin in this period are unpredictable and
close monitoring is essential, especially in the unconscious
or sedated patient.
Diabetic patients established on longer-acting insulin are
at risk of hypoglycaemia if regular food intake is interrupted, and of lipolysis and proteolysis if insulin therapy is
delayed. Postoperative wound healing and infection may be

Perioperative therapy
Type 2 diabetics not receiving insulin and undergoing minor
surgery usually can be managed satisfactorily without
insulin.108 However, diabetic patients scheduled for major
surgery, who are receiving hypoglycaemic medication or
who have poor glycaemic control, should be established on
insulin therapy preoperatively. Continuous i.v. infusion of
insulin is a better option than intermittent s.c. bolus
regimens11 and, at least in perioperative cardiac surgical
patients, may be associated with improved outcome.27
Although intermittent i.v. bolus regimens are still used,87
this approach is difcult to recommend.38 45
Adsorption of insulin on to the surface of syringes, i.v.
uid bags and i.v. giving sets is an unavoidable problem. In
83

McAnulty et al.

inuenced by the adequacy of perioperative glycaemic

control.72 118

Glycosylated haemoglobin (HbAc1) measurement has no

value in the perioperative period but is a valuable guide to
long-term glycaemic control.31 If HbAc1 values have been
consistently >8% it is probable that microvascular complications of diabetes are present.

Options for the perioperative management of

diabetes
The main concern for the anaesthetist in the perioperative
management of diabetic patients has been the avoidance of
harmful hypoglycaemia; mild hyperglycaemia has tended to
be seen as acceptable. This has been attributed to the
difculties of measuring blood glucose when the reduced
level of consciousness perioperatively masks signs and
symptoms of hypoglycaemia. However, in the past decade
the availability of more accurate and easy-to-use glucose
monitors, with evidence that good glycaemic control
improves short-term outcome, makes the practice of
`permissive hyperglycaemia' unacceptable.
One survey of anaesthetic practice in the Oxford region of
the UK suggests that anaesthetists are likely to manage
hyperglycaemia in perioperative diabetic patients more
aggressively now than they did in 1985.22 However, of the
172 respondents in this survey, 22% still preferred to
maintain blood glucose at >10 mmol litre1 in diabetic
patients and 2% preferred a value of >13 mmol litre1. The
vast majority of respondents maintained glycaemic control
for type 1 diabetic patients undergoing major surgery with
glucose and insulin infusions, either separately or combined. Nearly 90% of respondents did not consider it
necessary, in type 2 diabetics undergoing minor surgery, for
there to be any greater intervention than omitting the usual
hypoglycaemic therapy and avoidance of glucose-containing i.v. solutions. Surprisingly, 17% of senior anaesthetists
had the same approach to type 2 diabetics undergoing major
surgery. Cost and inconvenience may inuence decisions
about the intensity of blood glucose management and, until
recently, there has been little evidence to support strategies
aimed at tightening glycaemic control.35 Between the two
extremes of a diet-controlled stable type 2 diabetic
presenting for minor surgery and the `brittle' type 1 patient
undergoing major abdominal surgery, about whom there is
little argument, there remains considerable disagreement
about the ideal regimen for managing blood glucose.

Anaesthetic technique and the diabetic

patient
Anaesthetic techniques, particularly the use of spinal,
epidural, splanchnic or other regional blockade, may
modulate the secretion of the catabolic hormones and any
residual insulin secretion. The perioperative increase in
circulating glucose, epinephrine and cortisol concentrations
found in non-diabetic patients exposed to surgical stress
under general anaesthesia is blocked by epidural anaesthesia.39 125 The perioperative infusion of phentolamine, a
competitive a-adrenergic receptor blocking drug, decreases
the glycaemic response to surgery by partially reversing the
suppression of insulin secretion.75 Interestingly, a small
study of non-diabetic patients showed preservation of the
insulin response to a bolus of glucose after the use of low,
but not high, spinal anaesthesia.40 This implies that basal
islet cell secretion is maintained by b-adrenergic stimulation. Whether extensive spinal blockade is detrimental in
type 2 diabetics is not known. Cataract surgery in type 2
patients using local analgesia, when compared with general
anaesthesia, was associated with much less disruption of
glucose metabolism: blood glucose, lactate, b-hydroxybutyrate, serum cortisol, insulin and plasma non-esteried
fatty acid concentrations were measured perioperatively.3
Diabetic patients undergoing surgery with neural blockade will usually resume oral intake earlier than after general
anaesthesia. It is now common practice in cataract surgery
to allow normal oral intake and hypoglycaemic therapy
throughout the perioperative period. In a series of 12 000
cataract extractions under local anaesthesia, in which
patients were not starved, eight patients showed evidence
of brain stem anaesthesia, and one developed cerebral
spread of local anaesthetic solution. In only one patient was
surgery postponed because of persistent nausea.43 However,
the possibility of having to convert a regional technique to
general anaesthesia may militate against this practice in
other forms of surgery. At present, there is no evidence that
regional anaesthesia alone, or in combination with general
anaesthesia, confers any benet in the diabetic surgical
patient, in terms of mortality and major complications.
Regional anaesthesia may carry greater risks in the
diabetic patient with autonomic neuropathy. Profound
hypotension may occur with deleterious consequences in a
patient with co-existing coronary artery, cerebrovascular or
renovascular disease. The risks of infection and vascular
damage may be increased with the use of regional
techniques in diabetic patients; epidural abscesses occur
more commonly following spinal and epidural anaesthe-

Monitoring techniques
The advent of semi-automated devices has improved the
accuracy of measurement of blood and capillary glucose
concentrations in both the community and hospital.7 For
these machines to be effective they must be calibrated
regularly and people using them must be trained.
Recent work has suggested that measurement of circulating b-hydroxybutyrate concentrations may be helpful in
treating acutely unstable diabetes70 124 and the development
of a bedside device will enable the usefulness of sequential
estimations of ketonaemia to be assessed.70
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Diabetes mellitus

sia.54 77 Conversely, a diabetic peripheral neuropathy

presenting after epidural anaesthesia may be confused
with an anaesthetic complication of regional blockade.50

with difcult laryngoscopy and intubation. Stiffness of the

fourth and fth interphalangeal joints is a common feature
and the resulting alteration in palm print may be a good
predictor of difcult intubation.74 However, in one retrospective review of the anaesthetic records of 725 patients
who underwent renal and/or pancreatic transplantation (of
whom 209 were diabetic), none were reported as having
`moderate to extreme difculty' of laryngoscopy. A total of
4.8% of the diabetics presented `minimal to moderate'
difculty for intubation compared with 1.0% of the nondiabetics. All were intubated successfully although one was
intubated electively with the aid of a bre-optic exible
laryngoscope.120

Anaesthetic agents and diabetes

Induction agents may affect glucose homeostasis perioperatively. Etomidate blocks adrenal steroidogenesis and hence
cortisol synthesis, by its action on 11b-hydroxylase and
cholesterol cleavage enzymes, and consequently decreases
the hyperglycaemic response to surgery by approximately 1
mmol litre1 in non-diabetic subjects.26 The effects on
diabetic patients have not been established.
Benzodiazepines decrease the secretion of ACTH, and so
the production of cortisol, when used in high doses during
surgery.18 They reduce sympathetic stimulation but, paradoxically, stimulate growth hormone secretion and result in
a decrease in the glycaemic response to surgery. These
effects are minimal when midazolam is given in usual
sedative doses, but may be relevant if the drug is given by
continuous i.v. infusion to patients in intensive care.
High-dose opiate anaesthetic techniques produce not only
haemodynamic, but also hormonal and metabolic stability.
These techniques effectively block the entire sympathetic
nervous system and the hypothalamicpituitary axis, probably by a direct effect on the hypothalamus and higher
centres.36 Abolition of the catabolic hormonal response to
surgery will, therefore, abolish the hyperglycaemia seen in
normal patients and may be of benet in the diabetic
patient.59
Halothane, enurane and isourane, in vitro, inhibit the
insulin response to glucose in a reversible and dosedependent manner.19 32 The effect of propofol on insulin
secretion is not known. Diabetic patients show a reduced
ability to clear lipids from the circulation.123 Although this
is unlikely to be relevant during short anaesthetics when
propofol is used for maintenance or as an induction agent
only, it may have implications for patients receiving
propofol for prolonged sedation in the intensive care unit.

Coronary heart disease

Diabetic men are more than four times as likely, and women
ve times as likely, to have coronary heart disease (CHD)
than non-diabetics.15 The annual cardiac event rate for
untreated patients is 2.5% and even treated patients have
more aggressive coronary disease and experience worse
outcomes at any stage of the disease.96 Some patients may
have signicant CHD causing myocardial ischaemia and
even suffer myocardial infarction without typical symptoms. This may result from autonomic neuropathy,67 but
such `silent ischaemia' is unlikely to occur without the coexistence of multiple risk factors. However, even selective
screening targeted at patients with specic multiple risk
factors has been discouraged because there is no evidence to
support intervention (in the form of angioplasty or surgery)
for asymptomatic diabetic patients.99 What is the anaesthetist to do when presented with an asymptomatic diabetic
patient who has some or all of the other risk factors such as
advanced age, smoking, hyperlipidaemia and hypertension?
Perioperative management of such a patient may be altered
if it is known that there is a likelihood of myocardial
ischaemia even if intervention by coronary artery bypass
grafting or angioplasty (although perhaps not coronary
stenting) carries an unacceptable risk:benet ratio.81
Asymptomatic type 1 diabetics with severe nephropathy
scheduled for renal transplantation have been shown to
benet from preoperative screening and appropriate coronary revascularization.65 A similar strategy may well be
appropriate for high-risk diabetics, particularly those with
`metabolic syndrome', about to undergo major, elective
non-cardiac surgery.
Diabetic patients have a worse outcome after coronary
artery bypass surgery96 and tend to stay in hospital longer.60
They are more likely to develop postoperative renal
failure13 and suffer delayed stroke.46 Deep sternal wound
infection rates are also higher than in the non-diabetic
population,126 but the incidence may be reduced by
improving diabetic control with continuous insulin infusions.27 Mortality following coronary artery bypass surgery
in diabetics is generally reported as signicantly greater
than that in non-diabetics.110

Complications of diabetes
Microvascular, neuropathic and macrovascular complications of diabetes mellitus are of special concern for the
anaesthetist. Of particular importance are coronary heart
disease, diabetic nephropathy and autonomic neuropathy
because these may have a direct effect on the development
of perioperative complications. In addition, young patients
with long-standing type 1 diabetes and poor glycaemic
control were found to have signicantly decreased lung
volume, lung diffusing capacity and cardiac stroke index
during exercise when compared with patients treated with
intensive insulin therapy.78
Because of glycosylation of collagen in the cervical
joints, part of a generalized phenomenon called `stiff joint
syndrome',98 diabetic patients are more likely to present
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McAnulty et al.

pathy, there is loss of HRV. The severe impairment of HRV

in patients with end-stage diabetic nephropathy probably
results from autonomic neuropathy and partly from coexisting heart disease.57 The loss of HRV may be a
contributory risk factor for ventricular arrhythmias and
sudden death in these patients.57 The presence of autonomic
dysfunction in diabetics undergoing coronary artery surgery
is not, however, automatically associated with haemodynamic instability during induction and the cardiovascular
responses in non-diabetic and diabetic patients were very
similar.53
Diabetic gastroparesis is characterized by a delay in
gastric emptying without any gastric outlet obstruction.117
The increased amount of gastric contents enhances the risk
of acid aspiration during the induction of anaesthesia.82
These patients are often asymptomatic and unpredictable
difculties in tracheal intubation increase even further the
risk of aspiration.88 Studies have shown little effect of prokinetic agents, such as cisapride, in reducing the volume of
gastric contents in diabetics.89
Postoperative respiratory arrest seems to be more common in diabetic patients. Acute, unexpected respiratory
problems in the recovery room are more common in men, in
those aged >60 years, and in obese or diabetic patients.95

Diabetic nephropathy
In most countries, the leading causes of end-stage renal
failure are hypertension and diabetes mellitus. In the USA,
3040% of patients with type 1 diabetes will develop
diabetic nephropathy and end-stage renal failure.93 There is
now substantial evidence that angiotensin-converting enzyme (ACE) inhibitors have a renal protective effect in
patients with type 1 diabetes.61 This may also be the case in
type 2 diabetes, but the evidence is less convincing. No
agent has been shown to be renoprotective in the
perioperative period and some of the traditional drugs
used for this purpose may be harmful.17 105 Ensuring
adequate renal perfusion by expanding the extracellular
space (salt loading) or, more specically, the intravascular
space with appropriate haemodynamic monitoring may
reduce the risk of postoperative renal dysfunction.
Hydration with 0.45% sodium chloride solution alone
provides better protection against radiocontrast mediuminduced renal failure in at-risk subjects than saline with the
addition of furosemide or mannitol.102

Autonomic neuropathy
Diabetic patients frequently develop neuropathy, most
commonly a distal symmetrical sensory or sensorimotor
polyneuropathy with a variable degree of autonomic
involvement.12 Autonomic dysfunction, which is of particular importance to the anaesthetist, is detectable in up to
40% of type 121 and 17% of type 2 diabetic patients.23 Only
a small proportion of these patients are symptomatic, with
signs and symptoms such as gastroparesis, postural
hypotension, gustatory sweating, diabetic diarrhoea and
bladder paresis.121 Many pathogenic mechanisms have been
suggested for diabetic autonomic neuropathy, including
local ischaemia,112 tissue accumulation of sorbitol,20 altered
function of neuronal Na+/K+-ATPase pump activity103 and
immunologically mediated damage.21
The cardiovascular effects of insulin are paradoxical in
autonomic neuropathy patients. In normal subjects, i.v. or
s.c. insulin administration activates the sympathetic nervous
system, causing an increase in circulating norepinephrine,
supine arterial pressure and peripheral vascular resistance.85
At the supraphysiological concentrations often used in the
treatment of diabetes, vasodilation occurs with decreased
peripheral vascular resistance and increased ow.85 These
observations suggest that insulin has dual effects, namely a
vasoconstrictor effect mediated by the sympathetic nervous
system at low insulin concentrations, and a vasodilator
effect, perhaps mediated by nitric oxide release at higher
concentrations. In patients with autonomic neuropathy,
insulin causes a decrease in supine arterial pressure and
exacerbates postural hypotension.
Detection of autonomic neuropathy in patients without
symptoms has relied on methods such as assessment of heart
rate variability (HRV).104 In diabetic autonomic neuro-

Wound healing and infection

It has long been recognized that wound healing is impaired
in diabetic patients.9 44 This observation has been repeated
in animal models where it has been shown that pre- and
postoperative glycaemic control with insulin, not postoperative alone, can restore normal anastomotic healing.118
Recent work suggests that better glycaemic control with
insulin infusions may reduce the incidence of deep sternal
wound infections in diabetic patients who have undergone
cardiac surgery.27 This observation is supported by a study
demonstrating better preservation of neutrophil function
with `aggressive' glycaemic control using an insulin
infusion, compared with intermittent therapy, in diabetic
cardiac surgical patients.86 Interestingly, high-dose insulin
and glucose infusions, aimed at maintaining supranormal
plasma insulin concentrations and euglycaemia in nondiabetic burns patients, signicantly decreased donor-site
healing time after skin grafting.84

Conclusion
It is well known that diabetic patients are at greater risk of
perioperative mortality and morbidity after major surgery
and have a higher incidence of co-existing disease. Over
recent years evidence has accumulated that improving
glycaemic control in both the short and long term improves
outcome. Attention to detail in the day-to-day management
of the disease itself and associated conditions, such as
hypertension, reduces the devastating consequences of
microvascular and macrovascular complications. In add86

Diabetes mellitus

ition, a more aggressive approach to glycaemic control in

the perioperative period results in better wound healing,
lower morbidity and shorter hospital stays. Gone are the
days when anaesthetists could tolerate `permissive hyperglycaemia' with the idea that this approach was in the
patient's best interest. Tight metabolic control in the
perioperative period is imperative and is a goal which is
attainable in most patients.

17
18
19

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