Review Article

Perioperative Management of
Diabetes and Hyperglycemia in
Patients Undergoing Orthopaedic
Surgery

Ali A. Rizvi, MD
Shawn A. Chillag, MD
Kim J. Chillag, MD
From the Department of Internal
Medicine, University of South
Carolina School of Medicine,
Columbia, SC (Dr. Rizvi and
Dr. S. A. Chillag), and the Moore
Abstract
Persons with diabetes undergo more surgical procedures, have a
higher perioperative risk of complications, and have longer hospital
stays than do persons who do not have diabetes. Persons with
diabetes are frequently overweight, have a high prevalence of
cardiovascular risk factors, and are more likely to suffer from
chronic musculoskeletal conditions and traumatic injuries that
require orthopaedic attention. Surgery frequently disrupts usual
diabetes management, requiring adjustments to the treatment
regimen. Suboptimal perioperative glucose control may contribute
to increased morbidity, and it aggravates concomitant illnesses.
Many patients undergoing elective or urgent orthopaedic surgery
may have unrecognized diabetes or may develop stress-related
hyperglycemia in the hospital. The challenge is to minimize the
effects of metabolic derangements on surgical outcomes, reduce
glycemic excursions, and prevent hypoglycemia. Recent guidelines
advocate evidence-based glucose targets in the inpatient setting,
and regimens for intravenous and subcutaneous insulin are gaining
in popularity. Individualized treatment should be based on the
ambient level of glycemic control, outpatient treatment regimen,
presence of complications, nature of the surgical procedure, and
type of anesthesia administered. Management by a
multidisciplinary team and attention to discharge planning are key
aspects of care during and after orthopaedic surgery.

Orthopaedic Clinic, Columbia, SC
(Dr. K. J. Chillag).
None of the following authors or any
immediate family member has
received anything of value from or
owns stock in a commercial
company or institution related
directly or indirectly to the subject of
this article: Dr. Rizvi, Dr. S. A.
Chillag, and Dr. K. J. Chillag.
J Am Acad Orthop Surg 2010;18:
426-435
Copyright 2010 by the American
Academy of Orthopaedic Surgeons.
I
n critically ill surgical patients, di-
abetes mellitus is a risk factor for
adverse outcomes, including pro-
longed hospital stay and higher mor-
tality rates.1,2 Several observational
and interventional studies have indi-
cated that hyperglycemia is related to
adverse clinical outcomes in surgical
patients in the early postoperative
period.3,4 Undiagnosed diabetes and
hospital-induced hyperglycemia con-
tribute to increased postoperative
complications.5 Persons with hos-
pital-induced hyperglycemia are at
even greater risk than those with pre-
existing diabetes.6 Because of associ-
ated musculoskeletal complications,
patients with diabetes undergo more
surgical procedures than do patients
without diabetes.7 Diabetes is a ma-
jor risk factor for surgical site infec-
tion following orthopaedic spinal
operations,8 and it is associated with
increased postoperative complica-
tions, total hospital charges, and
length of stay after lumbar fusion.9

426 Journal of the American Academy of Orthopaedic Surgeons


The prevalence of diabetes and hy-
perglycemia in inpatients is estimated
to be between 5% and 30%.10 How-
ever, no reliable data exist for ortho-
paedic patients.
Evidence is accumulating that im-
proving blood glucose control in the
perioperative period can mitigate many
of the detrimental consequences of
hyperglycemia.11,12 Patients with dia-
betes frequently present with con-
comitant conditions that magnify
perioperative risk, including obesity,
hypertension, renal insufficiency, and
coronary artery disease.13 Surgery is
a stressful event that leads to tempo-
rary disruption of oral nutrition and
frequently requires adjustment of an-
tidiabetic therapy. The challenge is to
minimize the effect of metabolic de-
rangement on surgical complications
and the effect of the surgery on dia-
betes control. Factors that must be
taken into consideration include the
level of glycemic control and outpa-
tient treatment regimen, presence of
complications, nature of the surgical
procedure, inpatient glucose re-
sponses, and the type of anesthesia.14
There is an association between glu-
cose intolerance and preoperative
risk.
Surgical Stress and
Glucose Levels
The stress of surgery and anesthesia
leads to activation of a neuroendo-
crine response (Table 1). The secre-
tion of counterregulatory hormones
(eg, epinephrine, cortisol) antago-
nizes the action of insulin and predis-
poses to hyperglycemia and ketoaci-
dosis.15 Tachycardia, hemodynamic
instability, volume depletion, and the
common practice of reducing or
withholding insulin at a time of in-
creased demand may worsen the sit-
uation. Several pathophysiologic
pathways have been implicated, in-
cluding elevated insulin resistance,
July 2010, Vol 18, No 7
increased levels of inflammatory me-
diators, endothelial cell dysfunction,
defects in immune function, in-
creased oxidative stress, prothrom-
botic changes, and cardiovascular ef-
fects that contribute to impaired
ischemic preconditioning. Hypergly-
cemia has been shown to aggravate
or contribute to these underlying
mechanisms, whereas optimization
of glucose control has been shown to
reverse these deleterious changes.4
Surgical Risks and the
Benefits of Improved
Glucose Control
Patients with diabetes have more co-
morbid health conditions than does
the general population, including
obesity, hypertension, sleep apnea,
cardiovascular disease, congestive
heart failure, and undetected athero-
sclerosis (coronary, cerebral, and pe-
ripheral). Current guidelines desig-
nate the presence of diabetes as a
“cardiac risk equivalent.”16 Renal in-
sufficiency heightens problems of
fluid and electrolyte imbalance.17 Ef-
fects of neuropathic complications,
especially advanced cardiac, respira-
tory, and gastrointestinal autonomic
neuropathy, can lead to hemody-
namic instability, abnormal gut mo-
tility, and erratic glucose levels.18
Inadequate glucose control leads to
increased risk of infectious complica-
tions.1 The benefits of improved gly-
cemic control after open heart sur-
gery include a lower rate of deep
sternal wound infections, reduced
length of stay, and reduced hospital
cost.3 Decreased bloodstream and
nosocomial infections, acute renal
failure, ventilatory support, blood
transfusions, critical illness polyneu-
ropathy, and duration of stay in the
surgical intensive care unit have also
been demonstrated19 (Table 2).
Ali A. Rizvi, MD, et al
Table 1
Hemodynamic, Metabolic, and
Neuroendocrine Changes During
Surgery and Anesthesia in
Patients With Diabetes
Release of counterregulatory hormones
(ie, epinephrine, cortisol, growth
hormone)
Tachycardia and tendency to cardiac
arrhythmia
Vasoconstriction and labile blood
pressure responses
Elevated peripheral insulin resistance
Reduced insulin secretion
Enhanced hepatic gluconeogenesis
Decreased peripheral glucose utilization
Accelerated adipose tissue and protein
catabolism
Electrolyte abnormalities
Diabetes and Increased
Risk of Adverse Outcomes
in Orthopaedic Surgery
Diabetes is a risk factor for subopti-
mal perioperative outcomes in pa-
tients undergoing orthopaedic sur-
gery. Several studies have identified
the association between diabetes and
infectious complications after ortho-
paedic procedures.20,21 Lai et al22 re-
ported the presence of suboptimally
controlled diabetes in patients with
infected primary hip or knee arthro-
plasties. The perioperative complica-
tion rate in patients with diabetes
who undergo lumbar fusion is more
than twice that in patients with-
out diabetes (53% to 56% versus
21%, respectively).23 Patients with
diabetes also have an increased fre-
quency of complications, both major
(ie, wound infection, peripheral
nerve root lesion, cardiac arrhyth-
mia, acute renal failure, cerebrovas-
cular accident) and minor (ie, uri-
nary tract infection, ileus, electrolyte
deficiencies).9 The presence of diabe-
tes as a comorbid condition is associ-
ated with increased complication
rates after total knee arthroplasty.24,25
427
Perioperative Management of Diabetes and Hyperglycemia
Table 2
Relationship Between Improved Glycemic Control and Health Outcomes
Surgery or Event Outcome
Perioperative
Open heart Decreased rates of death, deep sternal wound infec-
tions, length of stay, cost
Surgical ICU Decreased mortality, bloodstream and nosocomial
infections, acute renal failure, ventilatory support,
blood transfusions, critical illness polyneuropathy, and
duration of ICU stay
Other
Acute coronary event Enhanced survival after myocardial infarction
Medical ICU Significant reduction in hospital mortality, transfusion
requirements, new cases of renal insufficiency, and
length of stay
Acute stroke Better neurologic outcome and enhanced functional
recovery
Labor and delivery Prevention of adverse effects of neonatal hypoglycemia
ICU = intensive care unit
Diabetes significantly increased mor- dial plasma glucose between 90 and
tality after total hip arthroplasty in a 130 mg/dL, and average postpran-
Finnish cohort study of 24,638 pa- dial plasma glucose <180 mg/dL.
tients.26 Residual functional disabil- Elective surgical procedures should
ity is also higher in diabetic patients be scheduled early in the day for pa-
who undergo surgery for lumbar spi- tients with diabetes. It may be advis-
nal stenosis27 and ankle fracture;28 able to delay elective surgery a few
glycemic control before, during, and weeks to a few months to obtain sat-
after surgery may play a significant isfactory glucose control.
role in these situations.
Cardiovascular disease can manifest
atypically, occur at a relatively young
Preoperative Management age, and remain asymptomatic in pa-
tients with diabetes.30 The surgeon
Patient Evaluation should have a low threshold for in-
depth evaluation of symptoms such as
Careful preoperative evaluation is es-
sential in patients with diabetes to chest pain, exertional dyspnea, and or-
identify previously unknown compli- thopnea; electrocardiography and stress
cations and manage known ones. For testing with or without cardiac imag-
elective surgery, it is prudent to orga- ing may be warranted in high-risk pa-
nize a multidisciplinary team that in- tients with multiple risk factors.31 Pa-
cludes the primary care physician tients with peripheral or cardiac
and, if necessary, an endocrinologist autonomic neuropathy are prone to
and a cardiologist. Glycemic targets intraoperative hypotension, perioper-
as close as possible to those advo- ative cardiac arrhythmia requiring
cated by the American Diabetes As- telemetry observation, gastroparesis,
sociation should be achieved before a hypoglycemia unawareness, and loss
planned surgical procedure.29 These of glucose counterregulation.18 The
targets include glycated hemoglobin presence of resting tachycardia, ortho-
(ie, A1C) <7.0%, average prepran- static hypotension, and loss of heart
428 Journal of the American Academy of Orthopaedic Surgeons
rate variability should signal the poten-
tial for intraoperative problems.
Serum creatinine level may not be a
sensitive indicator of true kidney func-
tion in elderly persons with diabetes. A
24-hour urine collection may be indi-
cated when there is an elevated serum
creatinine level, proteinuria, or concom-
itant long-standing or poorly controlled
hypertension. Insulin action is pro-
longed in renal impairment, promoting
glycemic unpredictability and hypogly-
cemia.
Pharmacologic Agents
The characteristics of currently avail-
able antidiabetic agents, including
the mechanism of action of various
classes, individual agents and their
brand names, duration of action,
dosing, and adverse effects, are sum-
marized in Table 3. Metformin and
sulfonylureas should be withheld 24
hours before surgery. The long-
acting sulfonylureas (eg, chlorpropa-
mide, glyburide) can cause pro-
longed hypoglycemia and should be
withheld for at least 48 to 72 hours.
Lactic acidosis is a rare but serious
side effect of metformin, especially in
elderly persons with compromised
kidney function. Metformin may be
restarted 48 hours after surgery pro-
vided that hemodynamic stability is
maintained and kidney function re-
mains normal.
The thiazolidinediones (TZDs [ie,
rosiglitazone, pioglitazone]) are
insulin-sensitizing agents that have
properties of fluid retention, intra-
vascular volume expansion, and di-
lutional anemia. They can precipitate
pulmonary edema and congestive
heart failure in susceptible patients,
especially when used in conjunction
with insulin. TZDs are contraindi-
cated in the presence of New York
Heart Association class 3 and 4 heart
failure. They should be restarted
only after postoperative recovery is
assured and there is no evidence of
 Ali A. Rizvi, MD, et al

Table 3
Overview of Oral Agents and Glucagon-like Peptide-1 Analogs for Diabetes by Drug Class
Drug Mechanism Agent Duration of Adverse Effects and
Class of Action (Brand Name) Action Dosing Precautions
Biguanides Reduce hepatic Metformin (Glucophage [Bristol- 12-18 h 500 mg with meals, increas- GI side effects: nausea, vomiting,
insulin resis- Myers Squibb, Lisle, IL], Glu- ing by 500 mg every 1-3 fullness, flatulence, diarrhea.
tance and glu- metza [Biovail Pharmaceuti- wk up to twice or three Rare life-threatening lactic aci-
cose produc- cals, Mississauga, ON, times a day. Optimally ef- dosis. Contraindicated in renal
tion Canada], Fortamet [First fective dose, 2,000 mg/d; insufficiency (serum creatinine
Horizon Pharmaceutical, maximum, 2,550 mg/d. level >1.4 in males and >1.2 in
Alpharetta, GA]) females).
Extended-release metformin 24 h 500 mg once per day; maxi- Same as above
(Glucophage XR [Bristol- mum dose, 2,000 mg
Myers Squibb]) once per day

Sulfonylureas Increase insulin Glyburide (Micronase [Pfizer,
secretion from New York, NY], DiaBeta
the pancreas [Aventis Pharmaceuticals,
Bridgewater, NJ], Glynase
[Pfizer])
Glipizide (Glucotrol [Pfizer], Glu-
cotrol XL [Pfizer])
Glimepiride (Amaryl [Aventis])
12-24 h Glyburide: 1.25-5.0 mg once Hypoglycemia, weight gain. Se-
or twice a day; maximum, vere hypoglycemia is a func-
20.0 mg/d tion of advanced age and renal
Glynase: 0.75-12.0 mg/d; insufficiency.
maximum, 12.0 mg/d
12-24 h 2.5-20.0 mg once or twice a Same as above
day; maximum, 40 mg/d
XL: 2.5-10.0 mg once or
twice a day; maximum, 20
mg/d
24 h 1-8 mg/d; maximum, 8 mg/d Same as above

Short-acting Enhance rapid- Repaglinide (Prandin [Novo 4-6 h 0.5-2.0 mg, 15-30 min be- Headache, dizziness, diarrhea. 3
secreta- phase insulin Nordisk Pharmaceuticals, fore each meal; increase times a day dosing and high
gogues release, re- Princeton, NJ]) weekly if necessary; maxi- cost may lead to compliance
duce postpran- mum, 16.0 mg/d issues.
dial glucose
Nateglinide (Starlix [Novartis 4-6 h 60-120 mg before each Same as above
Pharmaceuticals, Basel, Swit- meal
zerland])

Thiazo- Enhance insulin Rosiglitazone (Avandia [Glaxo- Days to weeks Start with 4 mg/d once or Weight gain, fluid retention,
lidinediones sensitivity in SmithKline, Philadelphia, PA]) twice a day; maximum, 8 edema, anemia, heart failure,
muscle, liver, mg/d possible increased cardiovas-
and fat cular risk with rosiglitazone.
Contraindicated with high-dose
insulin and in New York Heart
Association class 3 and 4 heart
failure.
Pioglitazone (Actos [Takeda Days to weeks 15, 30, or 45 mg once a Same as above
Pharmaceuticals, Deerfield, day; start with smaller
IL]) dose and titrate up

α-glucosidase Inhibit carbohy- Acarbose (Precose [Bayer, 2-3 h 25 mg/d; increase by 25 Modest glucose-lowering action.
inhibitors drate digestion Pittsburgh, PA]) mg/d every 4 wk to three Frequent GI side effects and
and delay glu- times a day (with first bite expense may limit compliance
cose absorp- of food) and utility.
tion
Miglitol (Glyset [Bayer]) 2-3 h 300 mg/d (150 mg/d when Same as above
weight <60 kg)

DPP-IV inhibi- Suppress the Sitagliptin (Januvia [Merck, 24 h 50-100 mg once a day Abdominal pain, fatigue, head-
tors enzyme that Whitehouse Station, NJ]) ache
breaks down
the incretin
hormone
GLP-1
Saxagliptin (Onglyza [Bristol- 24 h 2.5-5.0 mg once a day Same as above
Myers Squibb])

GLP-1 ana- Mimic the ac- Exenatide (Byetta [Amylin Phar- 6-8 h Start with 5 µg subcutane- Injection site pain and bruising,
logs tions of the maceuticals, San Diego, CA, ously 30 min before nausea, vomiting. Postmarket-
incretin hor- and Eli Lilly, Indianapolis, IN]) breakfast and dinner; in- ing reports of association with
mone GLP-1 crease to 10 µg after 2-3 acute pancreatitis.
wk if necessary
Liraglutide (Victoza [Novo 24 h Start with 0.6 µg subcutane- Injection site pain and bruising,
Nordisk]) ously, increase to 1.2 µg nausea, vomiting, diarrhea,
after 1 week and to a and headache. Slightly in-
maximum dose 1.8 µg if creased incidence of acute
necessary; inject without pancreatitis in human studies
regard to meals and medullary thyroid cancer in
rats.

DPP = dipeptidyl-peptidase, GI = gastrointestinal, GLP = glucose-like polypeptide

July 2010, Vol 18, No 7 429

Perioperative Management of Diabetes and Hyperglycemia

Table 4
Combination Oral Pills for Diabetes
Adverse Effects and
Drug Class Agent Ratios of Oral Agents and Dosing Precautions

Sulfonylureas and Glucovance (Bristol-Myers Ratios of glyburide and metformin: As for individual agents (see
biguanide Squibb, Lisle, IL) (glyburide 1.25:250 mg, 2.5:500 mg, 5.0:500 Table 3)
and metformin) mg. Start with 1.25:250 mg once or Side effects of more than one
twice a day, increasing every 2 wk, to medication
an average dose of 7.5:1,500 mg. Hypoglycemia risk with
Maximum dose should not exceed 20 sulfonylurea-based combina-
mg glyburide:2,000 mg metformin tions
daily.
Metaglip (Bristol Myers- Ratios of glipizide and metformin: 2.5: Same as above
Squibb) (glipizide and 250 mg, 2.5:500 mg, 5.0:500 mg.
metformin) Start with 2.5:250 mg once or twice a
day, increasing every 2 wk. Maximum
dose should not exceed 20 mg glipi-
zide:2,000 mg metformin daily.
Thiazolidinedione Avandamet (GlaxoSmithKline, Ratios of rosiglitazone and metformin: Same as above
and biguanide Philadelphia, PA) (rosiglita- 1.0:500 mg, 2.0:500 mg, 4.0:500 mg,
zone and metformin) 2.0:1,000 mg, 4:1,000 mg twice a
day. Dosage individualized based on
current therapy. Maximum, 8:2,000
mg/d.
ACTOplus Met (Takeda Phar- Ratios of pioglitazone and metformin: Same as above
maceuticals, Deerfield, IL) 15:500 mg, 15:850 mg
(pioglitazone and metformin)
Thiazolidinedione Avandaryl (GlaxoSmithKline) Ratios of rosiglitazone and glimepiride: Same as above
and sulfonylurea (rosiglitazone and glimepir- 4 mg:1 mg, 4 mg:2 mg
ide)
Duetact (Takeda Pharmaceu- Ratios of pioglitazone and glimepiride: Same as above
ticals) (pioglitazone and 30 mg:2 mg, 30 mg:4 mg
glimepiride)
DPP-IV inhibitor Janumet (Merck, Whitehouse Ratios of sitagliptin and metformin: Same as above
and biguanide Station, NJ) (sitagliptin and 50 mg:500 mg, 50 mg:1,000 mg
metformin)

DPP = dipeptidyl-peptidase

cardiopulmonary compromise or
fluid overload.
The recently introduced incretin-
based treatments are becoming pop-
ular as add-on medications in pa-
tients who do not achieve glucose
goals with traditional oral therapy.
These include exenatide, adminis-
tered by daily subcutaneous (SC) in-
jection, and the oral agent sitagliptin.
Patients should discontinue these
drugs 24 to 36 hours before surgery
and reinstitute them close to, or af-
ter, discharge from the hospital.
Many patients with type 2 diabetes
who present for orthopaedic surgery
may be receiving treatment with two
or more antihyperglycemic agents
that work through different but com-
plementary mechanisms of action.
Single-tablet combinations of two
oral drugs have been marketed under
several brand names and contain sul-
fonylureas, metformin, TZDs, and
sitagliptin in various ratios (Table 4).
These tablets offer convenience and
cost savings to the patient while
potentially improving compliance.
Contraindications and precautions
for these combinations are the same
as for their individual components.
Insulin remains the mainstay of treat-
ment for inpatient and perioperative hy-
perglycemia. It is powerful, immediately
effective, has few contraindications or
drug interactions, and is the preferred
medication in critically ill patients and
in those with hepatorenal disease, car-
diovascular limitations, or hemody-
namic compromise. Table 5 displays the
different insulin preparations, their on-
set and duration of action, and dosing.
In the ambulatory setting, a basal-bolus
regimen of long-acting (ie, basal) insu-
lin (eg, glargine, neutral protamine
Hagedorn [NPH]) combined with a
premeal short-acting (ie, bolus) insulin
(eg, regular, lispro, aspart) is commonly
used, especially in type 1 diabetes. Such
an approach with multiple daily insu-
lin injection is also being used in many
patients with type 2 diabetes, and it may
be continued as begun or in a modified
manner during the perioperative period.
A common practice in patients with
type 2 diabetes is to use once- or twice-
daily long-acting insulin in combination
with oral agents. Premixed insulins in
fixed ratios (ie, 70:30, 50:50) are widely
used, as well. No matter their therapeu-

430 Journal of the American Academy of Orthopaedic Surgeons

 Ali A. Rizvi, MD, et al

Table 5
Characteristics of Currently Available Insulin Preparations
Insulin Preparations Onset Duration of Dosing and
Type (Brand Name) of Action Peak (h) Action (h) Comments

Rapid-acting Lispro (Humalog, Eli
analogs Lilly, Indianapolis, IN)
Aspart (Novolog, Novo
Nordisk, Princeton, NJ)
Glulisine (Apidra, sanofi
aventis, Bridgewater,
NJ)
Short-acting hu- Humulin R (Eli Lilly)
man regular Novolin R (Novo Nor-
disk)
Intermediate-acting Humulin N (Eli Lilly)
human NPH Novolin N (Novo Nor-
disk)
Long-acting Glargine (Lantus, Aven-
analogs tis Pharmaceuticals,
Bridgewater, NJ)
Detemir (Levemir, Novo
Nordisk)
Human premixed Humulin 70/30
Novolin 70/30
Humulin 50/50
Novolin 50/50
Analog biphasic Humalog Mix 75/25 (Eli
Lilly)
Novolog Mix 70/30
(Novo Nordisk)
Humalog Mix 50/50
Novolog Mix 50/50
5-15 min 1-2 4-6 Given ≤15 min before
eating. Mimics natural
bolus insulin release.
Used in pumps.
30-60 min 2-4 6-8 Given 20-30 min before
meals. May cause late
postmeal hypoglycemia.
2-4 h 4-10 12-20 Once or twice daily dos-
ing. Peak may cause
variability of action.
2-4 h Flat ≈24 Peakless, with low risk of
hypoglycemia. Glargine
dosed once daily.
1-3 h ≈20 Dosed once or twice daily
30-60 min Twin-peaked: 2-4 12-20 Usually dosed 20-30 min
and 4-10 before meals twice
daily. Convenient but
rigid mix of bolus and
basal.
5-15 min Biphasic: 1-2 and 8-16 Given ≤15 min before
4-10 meals twice daily.
Slightly lower hypogly-
cemia risk compared
with human premixed
insulins.

NPH = neutral protamine Hagedorn

tic regimen, insulin-treated patients
should monitor their glucose readings
multiple times a day—before meals, 2
hours postprandially, and at bedtime—
for several weeks preoperatively. This
information is used to optimize preop-
erative glycemic control.
Perioperative Diabetes
Care During Major
Orthopaedic Surgery
Target Blood Glucose
Levels in the Hospitalized
Patient
The optimal range of blood glucose
levels in hospitalized patients has not
been determined and remains contro-
versial. No consensus exists on glyce-
mic goals for the perioperative peri-
od; however, several organizations
have established general targets for
hospitalized patients.11,12 The re-
cently reported findings from the
multinational Normoglycemia in In-
tensive Care Evaluation–Survival Us-
ing Glucose Algorithm Regulation
(NICE-SUGAR) trial are particularly
relevant.32 Intensive and conven-
tional glycemic control were com-
pared in 6,104 patients in the inten-
sive care unit. Intravenous (IV)
insulin was used to achieve a blood
glucose level of 81 to 108 mg/dL in
the intensive group and 144 to 180
mg/dL in the conventional group.
Surprisingly, there was an absolute
increase in the rate of the primary
end point, death at 90 days, with in-
tensive glucose control compared
with conventional control (27.5%
versus 24.9%; P = 0.02). As ex-
pected, there was a significantly
higher rate of severe hypoglycemia in
the intensive-control group (6.8%
versus 0.5%; P < 0.001).
A consensus statement of the
American Association of Clinical En-
docrinologists and the American Di-
abetes Association has since recom-
mended revising glucose targets as
follows: in critically ill patients, start
treatment at a threshold of ≤180 mg/
dL, preferably with IV insulin ther-
apy, and maintain the glucose level
between 140 and 180 mg/dL.33

July 2010, Vol 18, No 7 431

Perioperative Management of Diabetes and Hyperglycemia
Greater benefit may be realized at
the lower end of this range. Targets
<110 mg/dL are not recommended.
In patients who are not critically ill,
the recommendations are based on
clinical experience and judgment;
premeal glucose targets should gen-
erally be <140 mg/dL in conjunction
with random glucose values <180
mg/dL, as long as these targets can
be safely achieved. Thus, a reason-
able general target for the hospital-
ized orthopaedic patient undergoing
surgery is 110 to 180 mg/dL. These
goals should be flexible and individ-
ualized to the particular patient and
the clinical circumstances. Persis-
tently elevated readings indicate that
the treatment regimen must be ad-
justed or changed and should alert
the treating physician of the need to
explore the possible reasons for hy-
perglycemia.
Intraoperative Glucose
Management and
Postoperative Care
Hyperglycemia during major ortho-
paedic procedures, such as in spinal,
pelvic, hip, and knee surgery, is best
managed with a continuous IV insu-
lin infusion,21 with a separate 5%
dextrose solution (D5) 0.5NS or
D5NS drip at 100 to 125 mL/h. In
constituting the insulin drip, 100 U
regular insulin is added to 100 mL of
IV fluid, thus achieving a concentra-
tion of 1 U/mL. This is given via an
infusion device at the desired rate. A
reasonable guide for calculating the
initial hourly drip rate is to divide
the total outpatient amount by 24.
Alternatively, an empirical starting
rate is 0.02 U/kg/h,34 titrated subse-
quently to the goal glucose range.
The infusion and drip should be
started well in advance of the proce-
dure (preferably 2 to 3 hours before)
to allow titration to the desired glu-
cose range. Hourly fingerstick glu-
cose readings are done intraopera-
432
tively to help adjust the insulin rate
to the glycemic targets and to moni-
tor for hypoglycemia. Patients who
are undergoing elective major sur-
gery and whose blood glucose is
well-controlled (as reflected by fin-
gerstick readings and A1C values)
without the use of insulin in the out-
patient setting may not require an in-
sulin drip and can be managed with
SC supplemental insulin therapy.
Postoperatively, the insulin infusion
is converted to SC insulin injections af-
ter the effects of general anesthetics
abate and once the patient is hemody-
namically and metabolically stable and
is eating. When transitioning from IV
to SC insulin, the drip should not be
stopped until 30 to 60 minutes after the
first SC dose of long-acting (basal) in-
sulin has been given. Failure to overlap
IV and SC insulin can result in extreme
hyperglycemia or diabetic ketoacidosis
(DKA).
Currently, patients who need daily
SC insulin in the postoperative pe-
riod are managed according to the
principles of basal-bolus insulin ad-
ministration.35 Long-acting insulin is
combined with rapid-acting insulin.
The former should be started early
and the dose adjusted as necessary.
Mealtime requirements should be
met with individualized doses of
rapid-acting bolus insulin. In this re-
gard, it is advisable to think in terms
of supplemental or “correction” in-
sulin for above-target premeal glu-
cose readings, combined with “pran-
dial” insulin for food coverage.
These principles are illustrated in
Figure 1, which shows a sample SC
insulin regimen composed of both
long- and short-acting insulins.
Diabetes Management
During Minor Surgical
Procedures
For outpatient surgery that does not
require general anesthesia but that
Journal of the American Academy of Orthopaedic Surgeons
necessitates withholding oral food
intake, including arthroscopic proce-
dures, oral agents are held preopera-
tively, and supplemental short-acting
SC insulin is given when blood glu-
cose is >180 mg/dL. A D5 0.5NS or
D5NS drip at 100 mL/h is main-
tained, and blood glucose is checked
every 2 to 3 hours during and after
the procedure. Oral medications or
SC insulin are restarted when enteral
nutrition is reestablished.
Insulin-treated patients undergoing
ambulatory surgery are instructed to
take two thirds of their usual dose of
long-acting insulin preoperatively the
morning of the surgery.36 Blood glu-
cose is measured before surgery and
every 2 to 3 hours during surgery
and is treated with SC short-acting
insulin if the value is >180 mg/dL. A
solution of 5% dextrose in water
(D5W) drip at 100 mL/h is started
and continued should the patient ex-
perience nausea or vomiting after the
procedure. When oral feedings are
resumed, the usual doses of long-
acting and bolus insulin are reinsti-
tuted as early as possible, and blood
glucose levels are monitored before
meals and bedtime.
Inpatient Hypoglycemia
Among clinicians and nurses, fear of
inpatient hypoglycemia is prevalent
and is a significant barrier to intensi-
fication of glycemic control and at-
tainment of normoglycemia. Most
inpatient hypoglycemia is predict-
able, avoidable, and manageable,
and it should not be a limiting factor
in managing diabetes.37 Factors pre-
disposing to hypoglycemia include
advanced age, hypoglycemia un-
awareness or an altered ability to re-
port hypoglycemic symptoms, renal
insufficiency or dialysis, liver disease,
malnutrition, sepsis, and congestive
heart failure. Use of oral sulfonyl-
urea agents in elderly patients who
 Ali A. Rizvi, MD, et al

are prone to hepatorenal insuffi- Figure 1

ciency, polypharmacy, or drug inter-
actions may be contributory factors.
Insulin errors and omissions are
common. Insulin is one of the major
high-risk medications in the inpa-
tient setting.38 Most medication er-
rors can be traced to inadequate
knowledge of insulin pharmacoki-
netics, poor coordination and com-
munication, and lack of dose verifi-
cation requirements. Implementation
of automatic, nurse-driven hypogly-
cemia protocols for prevention and
treatment can ensure standardization
of quality.39 Examples of standing or-
ders (improper) in case of unex-
pected transport from the nursing
unit or interruption of nutrition are
as follows: “Hold prandial insulin if
nutrition interrupted,” and “If tube
feeds are stopped, begin D10W at
former tube feed rate, and monitor
glucose every hour.” The occurrence
of hypoglycemic episodes can be
minimized by promoting a culture of
safety through a hospital-wide or
ward-based policy of education, mon-
itoring, and verification.39
Most guidelines require treatment
in patients with blood glucose <70
mg/dL. In patients who are conscious
Example of a standardized subcutaneous insulin order set.
and able to eat, the “rule of 15”
should be followed—that is, the pa-
tient should be given 15 g fast-acting
agent in elderly patients with renal omit their bedtime or morning long-
carbohydrate, blood glucose should
insufficiency. acting insulin dose is poor advice,
be checked 15 minutes later, and the
procedure should be repeated if the stemming from an undue fear of
level remains <70 mg/dL. Larger perioperative hypoglycemia and ig-
Important Considerations norance of the dangers of unre-
amounts of food given more fre-
quently can cause undesirable re- Patients with type 1 diabetes need strained hyperglycemia. Sliding scale
bound hyperglycemia. Patients who basal insulin to prevent the develop- insulin (SSI) is a popular method of
are not conscious or who cannot ment of dangerous hyperglycemia insulin administration. However, SSI
swallow should be treated with one and DKA.36 A good rule is to admin- represents retroactive coverage, man-
ampule (50 mL) of 50% dextrose ister two thirds of the usual basal in- ages hyperglycemia after it happens,
(D50) parenterally, or 1 mg glucagon sulin dose preoperatively. Supple- and leads to glycemic variability (ie,
subcutaneously or intramuscularly if mental SC short-acting insulin is hyperglycemia alternating with hy-
no immediate IV access is available. given during surgery based on finger- poglycemia).40 SSI should rarely be
Persistent hypoglycemia is more stick readings. An excellent alterna- used as the sole method of insulin ad-
commonly encountered as the result tive method of insulin administration ministration for a period longer than
of serious insulin dosing error or sec- is through the use of an IV drip. In- 24 to 48 hours, especially for a patient
ondary to the use of a sulfonylurea structing patients who use insulin to who requires substantial doses of insu-

July 2010, Vol 18, No 7 433

Perioperative Management of Diabetes and Hyperglycemia
lin coverage around the clock. Early
initiation of a basal-bolus insulin reg-
imen is recommended.
Previously undiagnosed diabetes or
so-called hospital-induced stress hyper-
glycemia carries the same poor progno-
sis as known diabetes and should be
treated in a similar fashion.5 It is also
important to establish a stable regi-
men of diet and pharmacologic ther-
apy well in advance of anticipated dis-
charge.12 Patients should be taught
basic survival skills by the diabetes
educator or nursing staff, particu-
larly if they are new to glucose self-
monitoring and insulin administra-
tion. Arrangements should be made
for an office visit with the primary
care physician within 2 weeks of dis-
charge to review and adjust the treat-
ment plan if necessary.
Special Situations
In emergent and trauma cases, gen-
eral principles of hemodynamic as-
sessment, fluid status, and electrolyte
balance should be followed.14 Undi-
agnosed diabetes and stress hyper-
glycemia may be encountered. Ex-
tremely elevated glucose levels and
the presence of acidosis should alert
the surgeon to the possibility of
DKA. Attention should be paid to
factors that can aggravate hypergly-
cemia, such as infection and acute
cardiovascular events. Adequate hy-
dration and the use of a continuous
variable-rate IV insulin infusion with
hourly monitoring are necessary for
major trauma and emergencies. Ev-
ery effort should be made to reach
glucose levels as close as possible to
the recommended targets in the peri-
operative and postoperative peri-
ods.16
Parenteral nutrition and tube feed-
ings before and after surgery may in-
crease insulin requirements dramatical-
ly; daily adjustment of the insulin drip
rate or basal insulin dose is usually nec-
434
essary. If supplemental short-acting in-
sulin is needed, a recommended strat-
egy is to add this correction amount to
the next day’s basal insulin dose to pre-
vent feeding-induced hyperglycemia.
Glucocorticoids can induce severe in-
sulin resistance and hyperglycemia, es-
pecially postprandially. Initiation of in-
sulin, either SC or IV, is commonly
required. Patients on insulin pump
treatment should continue on pump
therapy if they will remain awake,
alert, and able to operate it during mi-
nor or ambulatory surgery. For major
surgery and procedures that require an-
esthesia, the pump should be discontin-
ued and the patient switched to IV in-
sulin drip several hours before surgery.
Pump therapy can be reinstated post-
operatively when the patient is stable
and can reliably operate the pump. Pa-
tients should never be advised to stop
or disconnect pumps the night before
or the morning of surgery. Lack of in-
sulin delivery can precipitate extreme
hyperglycemia and DKA. Input from
the patient’s endocrinologist before and
during hospitalization is advisable.
Summary
Adequate diabetes management during
orthopaedic surgery requires close at-
tention to several factors: duration of
diabetes, degree of glycemic control,
presence and extent of complications,
outpatient treatment regimen, and type
of surgical procedure. In addition,
unique patient situations demand indi-
vidualization and flexibility of care.
Good glycemic control reduces the oc-
currence of adverse outcomes during
the perioperative period. Both hypogly-
cemia and hyperglycemia can prove to
be detrimental and should be avoided
by paying close attention to nutritional
changes and to the antidiabetic treat-
ment regimen, and by adhering to the
general principles outlined above. A cul-
ture of optimal management fostered
through awareness and education at all
Journal of the American Academy of Orthopaedic Surgeons
levels of surgical care in the hospital set-
ting is vital to achieving and maintain-
ing these objectives.
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