Protocol-directed insulin infusion sliding scales improve perioperative hyperglycaemia in critical care
Protocol-directed insulin infusion sliding scales improve perioperative hyperglycaemia in critical care
Man Lin Hui 2
Arun Kumar 1
Gary G Adams 0
0 Insulin and Diabetes Experimental Research (IDER) Group, Faculty of Medicine and Health Science, University of Nottingham , Clifton Boulevard, Nottingham NG7 2RD , UK
1 Faculty of Medicine and Health Science, University of Nottingham , Clifton Boulevard, Nottingham NG7 2RD , UK
2 The Queen Elizabeth Hospital , 30 Gascoigne Road, Kowloon , Hong Kong
Perioperative hyperglycaemia is associated with poor outcomes in patients undergoing cardiac surgery. Frequent postoperative hyperglycaemia in cardiac surgery patients has led to the initiation of an insulin infusion sliding scale for quality improvement. A systematic review was conducted to determine whether a protocol-directed insulin infusion sliding scale is as safe and effective as a conventional practitioner-directed insulin infusion sliding scale, within target blood glucose ranges. A literature survey was conducted to identify reports on the effectiveness and safety of an insulin infusion protocol, using seven electronic databases from 2000 to 2012: MEDLINE, CINAHL, EMBASE, the Cochrane Library, the Joanna Briggs Institute Library and SIGLE. Data were extracted using pre-determined systematic review and meta-analysis criteria. Seven research studies met the inclusion criteria. There was an improvement in overall glycaemic control in five of these studies. The implementation of protocols led to the achievement of blood glucose concentration targets more rapidly and the maintenance of a specified target blood glucose range for a longer time, without any increased frequency of hyperglycaemia. Of the seven studies, four used controls and three had no controls. In terms of the meta-analysis carried out, four studies revealed a failure of patients reaching target blood glucose levels (P < 0.0005) in the control group compared with patients in the protocol group. The risk of hypoglycaemia was significantly reduced (P <0.00001) between studies. It can be concluded that the protocol-directed insulin infusion sliding scale is safe and improves blood glucose control when compared with the conventional practitioner-directed insulin infusion sliding scale. This study supports the adoption of a protocol-directed insulin infusion sliding scale as a standard of care for post-cardiac surgery patients.
Hyperglycaemia; Perioperative; Protocol-directed insulin infusion; Sliding scales
Hyperglycaemia is a problem associated with blood
glucose levels in excess of 10 mmol/l; it is a common
occurrence in cardiac surgery patients and is associated
with adverse outcomes . Prolonged hyperglycaemia
increases the risk of infection and contributes to higher
mortality and morbidity. Mounting evidence documents
the beneficial effects of tight glycaemic control on
patients’ recoveries  and highlights the importance of
avoiding hyperglycaemic-related complications in
coronary artery bypass graft patients, for effective
postoperative glycaemic control.
Temporary hyperglycaemia during stress is often
helpful and helps to provide more glucose to prepare the
individual for action . However, hyperglycaemia in a
critically ill  or postoperative patient  may have
various detrimental effects on the host’s defence system:
blood glucose levels >180 mg/dl (10 mmol/l) have a
compromising effect on the immune system ; the
immune responsiveness of the mononuclear phagocytic
cells is depressed; neutrophil function is impaired; the
inflammatory response is exaggerated; and the immune
system is weakened, thus increasing susceptibility to
infection . Recent evidence has proved that
perioperative (intraoperative plus postoperative) hyperglycaemia is
directly correlated with the development of deep sternal
wound infection, increased mortality and morbidity, and
increased hospital stay . Furnary  reported that the
rate of wound infection was doubled when blood glucose
levels were between 180 mg/dl (10 mmol/l) and 216 mg/
dl (12 mmol/l), fourfold when they were between 216
mg/dl (12 mmol/l) and 252 mg/dl (14 mmol/l) and even
sixfold when over 252 mg/dl (14 mmol/l); when blood
glucose levels were maintained at below 180 mg/dl (10
mmol/l), there was no increase in the rate of wound
Treating hyperglycaemia in hospitalized patients has
proven to be beneficial . However, normoglycaemia
after cardiac surgery is usually difficult to maintain and
requirements for insulin after cardiac surgery with
cardiopulmonary bypass are much higher than after other
Because the use of the cardiopulmonary bypass
machine necessitates the administration of catecholamines
and corticosteroids during and after cardiac surgery, the
patient’s insulin resistance status changes continuously,
thus altering the patient’s insulin response and causing
fluctuations in glycaemia.
Recognizing the detrimental impact of hyperglycaemia
on postoperative surgical wound infection and the
importance of glycaemic control in cardiac surgery patients
is important and appropriate in managing
hyperglycaemic control. To address this issue, a systematic
review was carried out to examine the effectiveness and
safety of the protocol-directed insulin infusion sliding
scale variable rate intravenous insulin infusion on this
Design of the study
The electronic databases MEDLINE and CINAHL were
searched to identify keywords and index terms used in
describing relevant studies. Keywords used in the
preliminary searching process included: ‘insulin infusion
sliding scale’, ‘open-heart surgery’, ‘practitioner-directed’
A more detailed and extensive search was then
conducted across a number of electronic databases to
ensure that the majority of studies within the inclusion
criteria were recruited (Figure 1). Databases that cover
the healthcare literature and clinical trials were searched.
To increase the coverage of all relevant evidence,
different databases were used in the searching process:
MEDLINE, CINAHL, the Cochrane Library, the Joanna
Briggs Institute (JBI) Library, and EMBASE. To identify
published studies that are not available electronically,
hand searching was also done. In addition, as it can take
more than a year for some studies to be published, and
these studies may not be searchable in electronic
databases, a manual journal search was also performed.
Unpublished studies were sought, to overcome or
reduce publication bias, using the System of Information
on Grey Literature in Europe (SIGLE) database.
The bibliographies and reference lists from the
recruited articles were consulted to identify additional
studies for possible inclusion in this review.
The outcomes of interest are the effectiveness and
safety of the insulin infusion sliding scale in controlling
blood glucose level. The efficiency of an insulin infusion
sliding scale in controlling blood glucose levels and
reducing them to within the normal range plays a large
role in dictating the scale’s use in clinical practice. So
efficiency was set as one of the outcome of interest. In
addition, any insulin infusion sliding scale used to lower
the blood glucose level may induce hypoglycaemia,
which can lead to devastating effects, such as irreversible
neurologic deficit . Therefore, safety of an insulin
infusion scale is another important factor that needs to be
taken into consideration.
To prevent publication bias, all published and
unpublished studies that were written in English and met the
inclusion criteria were included. In addition, to identify
only the most up-to-date studies, only those published
after 2000 were included.
Type of participant
All adult patients, over 18 years old who had undergone
open-heart surgery with blood glucose level >180 mg/dl
(10 mmol/l) and needed insulin therapy, with or without
comorbidities will be eligible for inclusion, except those
patients who developed diabetes ketoacidosis.
Of the 239 potentially relevant articles identified during
the primary search, and after screening all titles and
abstracts, 229 clearly did not meet the inclusion criteria
and were therefore excluded. Hard copies of all potentially
relevant articles were retrieved, including those obtained
directly from the search (n = 10) and those obtained
through reference lists (n = 7). Irrelevant articles were
excluded after detailed evaluation of the full text (Figure 1).
There was usually more than one reason for excluding
each study from the analysis; these included:
1) Not all participating patients received protocol
directed blood glucose management (67 articles).
2) There was an irrelevant comparison group, (for example, a computer-based algorithm was used instead of a control group) (21 articles).
Potentially relevant articles identified
Hard copies of all potentially relevant
1) through the above search (n=10) AND
2) siftingthroughreferencelists (n=7)
(total = 17)
Clearly not meeting the inclusion criteria after
screening for all titles and abstracts (n=229):
8) Targetbloodglucose higher 67 21 64
1) Population mixed with other medical and surgical patients
2) Irrelevant comparison
3)Target blood glucose higher
than 180mg/dL (10mmol/L)
Figure 1 Flowchart of study selection. The data in this figure refer to the original search, completed in 2011.
3) Data from one study were used in more than one publication (in the form of quality of life data) (64 articles).
4) The population studied included other medical and surgical patients (28 articles).
5) The report studied a paediatric population (26 articles).
6) The patients studied were receiving diabetes ketoacidosis care (9 articles).
7) There were missing data for patients receiving study medication (4 articles).
8) The target blood glucose was higher than 180 mg/dl (10 mmol/l) (10 articles). This left seven studies eligible for systematic review (Table 1).
Description of interventions
Interventions of interest will be limited to the use of the
protocol-directed insulin infusion sliding scale; (2) a
newly developed insulin infusion protocol; or a protocol
modified from an existing protocol. For comparison, a
practitioner-directed insulin infusion sliding scale and a
conventional simple insulin infusion sliding scale will be
included. Studies examining other types of insulin
infusion sliding scale (such as computer-directed scales) will
Table 1 Protocol-directed insulin infusion improve perioperative hyperglycaemia in critical care
Tamaki et al. 40 cardiac
(2008)  surgery
A nurse-driven insulin infusion
protocol was developed and
implemented in postoperative
cardiothoracic surgical intensive
care patients with or without
This before-and-after cohort
study used two periods of
measurement: a 6-month
baseline period prior to the
initiation of the insulin
infusion protocol (control
group, n = 174) followed by a
6-month intervention period, in
which the protocol was used
(protocol group, n = 168).
The Yale insulin infusion
protocol was modified by
taking into consideration the
characteristics of Japanese
diabetics and the hospital
The modified protocol was
tested in 40 type-2 diabetic
patients after elective
openheart surgery, compared with
35 type-2 diabetic patients
under empirical blood glucose
Frequency of Frequency of
(7.1%) <40 mg/
dl (2.2 mmol/l)
Findings showed percentage
and time of blood glucose
measurements within the tight
glycaemic control range
(control 47% vs. protocol 61%;
P = 0.001),
28 patients Area under curve (AUC) of
(16.7%) <65 mg/ glucose exposure >150 mg/dl
dl (3.6 mmol/l) (8.3mmol/l) vs. time for the first
24 hours of the insulin infusion
(control 28.4 vs. protocol 14.8; P
< 0.001), median time to blood
glucose <150 mg/dl (8.3mmol/
l) (control 9.4 h vs. protocol
2.1h; P < 0.001), and
percentage blood glucose <65
mg/dl (3.6 mmol/l) as a marker
for hypoglycaemia (control
9.8% vs. protocol 16.7%; NS).
values <60 mg/
0.5% ± 5.9%
Analyses of 1,656 blood
glucose measurements during
insulin infusion revealed that
the percentage of samples that
showed achievement of target
blood glucose level (80 to 140
mg/dl (4.4 to 7.8 mmol/l)) was
higher under protocol (78 ±
15%, n = 870) than control (57
± 23%, n = 786, P < 0.0001).
On the other hand, the fraction
of samples with blood glucose
<60 mg/dl (3.3 mmol/l) was
comparable in the two groups
(protocol: 0.5 ± 5.9‰, control:
5.1 ± 18.5‰).
None of the patients with
significant clinical adverse
The insulin-resistance guided
protocol resulted in significant
increased percentage of time
spent in the normoglycaemic
range (82.5% vs. 65.8%,
P < 0.001), reduced rate of
hypoglycaemic episodes (0.12
vs. 0.99, P < 0.01), reduced rate
of hyperglycaemic episodes
(capillary blood glucose >126
mg/dl (7 mmol/l): 4.8 vs. 8.2,
P < 0.01), and reduced time to
the first measurement in the
target range. Total daily dose of
insulin was mildly increased,
glucose concentration; and
total daily dose of insulin
Patients with diabetes mellitus
or random blood glucose >150
mg/dl were treated in the
intensive care unit with
intravenous insulin, followed by
a multi-injection protocol
consisting of four
glargineaspart insulin injections in the
ward, with a glycaemic target
of 110 to 150 mg/dl (6.1 to 8.3
Table 1 Protocol-directed insulin infusion improve perioperative hyperglycaemia in critical care (Continued)
The study cohort (n = 410)
consisted of consecutive
cardiothoracic surgery. Control
patients (n = 207) were
admitted during the first 8
The intervention group of
patients (n = 203) were
operated on during the
following 8 months.
The main outcome measures
were glycaemic control and the
rate of postsurgery infection.
(0.2%) <60 mg/
dl (3.3 mmol/l)
but failed to reach statistical
significance (92.48 vs. 82.64
units, P = 0.32).
During the intervention, mean
blood glucose ± SD was 151 ±
19 mg/dl (8.4 ± 1.1 mmol/l)
and 157 ± 32 mg/dl (8.7 ± 1.8
mmol/l) in the intensive care
unit and ward, respectively, vs.
166 ± 27 mg/dl (9.2 ± 1.5
mmol/l) and 184 ± 46 mg/dl
(10.2 ± 2.6 mmol/l) during the
control period (P < 0.0001). The
incidence of hypoglycaemia
(blood glucose less than 60
mg/dl) was low and similar in
the two groups (2.5% control
vs. 3% intervention). Intensive
insulin treatment decreased the
risk for infection from 11% to
5% (56% risk reduction, P =
0.018), mainly by reducing the
incidence of graft harvest site
infection (6.9% vs. 2.5%, P =
0.034). The incidence of atrial
fibrillation after coronary artery
bypass graft surgery decreased
from 30% to 18% (39% risk
reduction; P = 0.042).
The insulin infusion protocol
was used 137 times in 118
patients. The median time
required to reach target blood
glucose levels (100 to 139 mg/
dl (5.6 to 7.7 mmol/l)) was 5
hours. Once blood glucose
levels decreased below 140
mg/dl, 58% of 2242 subsequent
hourly blood glucose values fell
within the target range, 73%
within a ‘clinically desirable’
range of 80 to 199 mg/dl (4.4
to 11 mmol/l). Only five (0.2%)
blood glucose values were less
than 60 mg/dl (3.3 mmol/l),
Table 1 Protocol-directed insulin infusion improve perioperative hyperglycaemia in critical care (Continued)
483 nondiabetics and 168
diabetics scheduled for cardiac
surgery with cardiopulmonary
bypass were recruited.
To anticipate rapid
perioperative changes in insulin
requirement or sensitivity
during surgery, a dynamic
algorithm presented in tabular
form, with rows representing
blood glucose ranges and
columns representing insulin
dosages based on the patients’
insulin sensitivity was
developed. The algorithm
adjusts insulin dosage based on
blood glucose level and the
projected insulin sensitivity (for
example, reduced sensitivity
during cardiopulmonary bypass
and normalizing sensitivity after
230 consecutive patients (mean
± SD age: 67 ± 11 years;
diabetic patients: n = 62)
undergoing cardiac surgery
(coronary artery bypass grafting:
n = 137; 20% off-pump) or
intrathoracic aortic (n = 10)
surgery were included.
with no associated adverse
value: 48 mg/dl
Blood glucose 18,893 blood glucose
values <60mg/dl measurements were made
(3..3 mmol/l) during and after surgery.
During surgery, the mean
glucose level in nondiabetic
patients was within targeted
levels except during (112 ± 17
mg/dl (6.2 ± 0.9mmol/l)) and
after rewarming (113 ± 19 mg/
dl (6.3 ± 1.1mmol/l)) on
In diabetics, blood glucose was
decreased from 121 ± 40 mg/dl
(6.7 ± 2.2 mmol/l) at
anaesthesia induction to 112 ±
26 mg/dl (6.2 ± 1.4 mmol/l) at
the end of surgery (P < 0.05),
with 52.9% of patients
achieving the target.
value: 40 mg/dl
In the intensive care unit, the
mean glucose level was within
the targeted range at all times,
except for diabetics on arrival
at the intensive care unit (113
± 24 mg/dl (6.3 ± 1.3mmol/l)).
Of all blood glucose
measurements (operating room
and intensive care unit), 68.0%
were within the target, with
0.12% of measurements in
nondiabetics and 0.18% in
diabetics below 60 mg/dl (3.3
mmol/l). Hypoglycaemia <50
mg/dl (2.8mmol/l) was avoided
in all but four (0.6%) patients
(40 mg/dl (2.2mmol/l) was the
lowest observed value).
All patients received
postoperative insulin therapy.
Patients spent 57.3% and 69.7%
of time within the blood glucose
target range on postoperative
days 1 and 2, respectively. The
percentage of time was
significantly higher in
nondiabetics than in diabetics.
Mean blood glucose
Table 1 Protocol-directed insulin infusion improve perioperative hyperglycaemia in critical care (Continued)
Blood glucose control was
managed according to an
insulin therapy protocol,
described by Goldberg et al.
, in use for 6 months. Insulin
infusion rate and frequency of
blood glucose monitoring were
adjusted according to: (1) the
current blood glucose
value; (2) the previous blood
glucose value; and (3) the
current insulin infusion rate.
Efficacy was assessed by the
percentage of time spent at the
target blood glucose level (100
to 139 mg/dl (5.6 to 7.7mmol/l))
intraoperatively and during the
first two postoperative days.
measurements per patient
postoperative days 1 and 2 were
4 ± 1, 10 ± 2 and 7 ± 2,
respectively. No patient
experienced any severe
hypoglycaemic events (blood
glucose <50 mg/dl (2.8mmol/l)).
Type of analysis
The objective of this study was to conduct a systematic
review to determine whether a protocol-directed insulin
infusion sliding scale is as safe and effective as the
practitioner-directed insulin infusion sliding scale in
bringing blood glucose values within the target range in
a practical and real-life setting.
To minimize any errors and subjective judgement in
the decision process, a critical appraisal instrument
developed from the Joanna Briggs Institute
(JBI-MAStARI) was used to appraise the methodological validity
and quality of the studies independently . This
checklist required the authors to rate each individual
study into one of three levels of credibility .
Data extraction was carried out by two reviewers
independently to minimize errors. Data were extracted and
stored using the standardized data extraction tool
developed by JBI-MAStARI. Inconsistency in extracted data
was settled by discussion between two reviewers. Where
an agreement could not be reached, the problem was
referred to a third reviewer for a decision.
Meta-analysis was carried out where appropriate and
pooled using meta-analytical methods within Review
Manager (RevMan) Version 5.1 software. No ethical
approval was needed for this study.
Permission was obtained to use the databases and data
within this study.
No ethical approval was required.
Results and discussion
Perioperative hyperglycaemia has been shown to be
associated with adverse surgical outcomes in cardiac
surgery patients [13,14]. Effective hyperglycaemic treatment
is, therefore, of significant benefit in all patients after
cardiac surgery . Here, we present the results of a
number of studies where protocol-directed insulin
infusions improve perioperative hyperglycaemia in critical
care. These are divided into those with and without the
use of controls in their studies.
The studies carried out by Zimmerman et al. ,
Tamaki et al. , Caddell et al.  and Leibowitz
et al.  all showed positive correlations between the
ability to attain target blood glucose levels and the infusion
regimen used when compared with the controls.
This is exemplified in the study of Zimmerman et al.
, who examined 168 (protocol group) and 174
(control group) patients in the cardiothoracic intensive care
unit. The results clearly showed that the target blood
glucose range was achieved within 2.1 hours of
treatment compared with those patients on the standard
sliding scale, where it took 9.4 hours to achieve the target
blood glucose range, a significance level of P < 0.001.
Moreover, 61% of all blood glucose measurements were
within the target range (protocol group) compared with
47% (control group). Furthermore, the protocol group
remained within the target range for longer (65.4%)
compared with the control group (54.6%).
The glycaemic level in the protocol group may be
lower than observed, owing to the administration of
corticosteroids and their ability to aggravate hyperglycaemic
status . Nevertheless, the results demonstrated that
implementation of the protocol led to a significant
improvement in glycaemic control. The speed with which
this control was achieved, however, is controversial
because this study was associated with the highest level of
hypoglycaemia among all seven studies. This indicates
that too-rapid lowering of blood glucose levels could be
dangerous in cardiac diabetic surgery patients, which is
supported by a randomized controlled trial of 10,251
patients that demonstrated that rapidly lowering blood
glucose concentrations in patients with type 2 diabetes
might harm patients by precipitating hypoglycaemia
. The safety of this particular protocol is, however,
called into question when 16.7% of patients in the
protocol group were subjected to levels of <65 mg/dl (3.6
mmol/l) or less compared with 9.8% of patients in the
In another protocol versus control study, Tamaki and
co-workers evaluated the effectiveness and safety of a
modified Yale insulin infusion protocol , to maintain
blood glucose levels at 80 to 140 mg/dl (4.4 to 7.8
mmol/l) in 40 Japanese diabetic patients who had
undergone cardiac surgery. The rate of change of insulin
infusion was modified to ensure effective and safe use for
Asian patients .
Once again, there was a positive correlation between
the treatments used in the protocol group compared
with those used in the control group. The patients in
the protocol group reached their target blood glucose
levels more quickly (3.1 ± 2.1 hours) compared with
the control group (5.0 ± 3.3 hours). In addition, of the
total 870 blood glucose measurements, 78 ± 15% were
within the target range (protocol group) compared
with 57 ± 23% of the total 786 measurements in the
control group (P <0.0001).
Although this supports the work carried out by
Zimmerman et al. , Tamaki’s work is still the only
study carried out on Asian cardiac surgery patients, and
it is difficult to correlate these results directly with those
carried out in countries that utilize alternative protocols.
Moreover, the small sample size of this study limited the
generalizability of this particular study and the ability to
capture the true clinical impact on this population.
Caddell et al.  introduced an insulin-resistance
guided protocol, which demonstrated similar findings to
those obtained in the Zimmerman and Tamaki studies.
Caddell’s group showed that the insulin-resistance
guided protocol led to more rapid and effective blood
glucose control in cardiac surgery patients with target
blood glucose levels of 80 to 110 mg/dl (4.4–6.1 mmol/l)
in the first 24 hour postoperative period.
In the protocol group, 65% of patients reached target
blood glucose ranges within 3 hours compared with 65%
of the patients (control group), who reached the target
range within 9 hours, (P < 0.01). Additionally, patients
in the protocol group maintained their blood glucose
concentration within the target range longer (82.5%
(19.8 hours)) than the control group (65.8% (15.7
hours)), a significance level of P < 0.001.
The principal strength of Leibowitz’s study  over
the Zimmerman, Tamaki and Caddell studies is the
comparatively large number of patients. The study cohort
consisted of 410 patients undergoing cardiothoracic
surgery. The control patients (n = 207) were admitted
during the first 8 months, whereas the intervention group
of patients (n = 203) were operated on during the
following 8 months.
The percentage of patients maintaining a target
blood glucose level of 110 to 150 mg/dl (6.1 to 8.3
mmol/l) was 55% (protocol group) and 39% (control
group) (P < 0.0001), although the effective
achievement of target blood glucose control resulted in a
small increase in the frequency of hypoglycaemia (3%
vs. 2.5%), which was not considered significant.
Nevertheless, the frequency of hypoglycaemia was
still lower than that observed in other studies, which
used the same target blood glucose range (110 to
150 mg/dl (6.1 to 8.3 mmol/l)) and was associated
with 5% of hypoglycaemic events in cardiac care unit
Three studies that were carried out without the use of
controls were those of Goldberg et al. , Lecomte et al.
 and Studer et al. . Although no controls were used,
insulin infusion protocols were used to obtain target blood
glucose levels of 100 to 139 mg/dl (5.6 to 7.7 mmol/l), 80
to 110 mg/dl (4.4 to 6.1 mmol/l) and 100 to 139 mg/dl
(5.6 to 7.7 mmol/l), respectively.
Goldberg’s group  investigated the use of an
insulin infusion protocol in 118 patients (protocol group).
The median time required to achieve the target
glycaemic level was 5 hours. When blood glucose levels fell
below 140 mg/dl (7.8 mmol/l), 58% of 2242 subsequent
hourly blood glucose values fell within the target range.
The strength and effectiveness of Lecomte’s study 
stemmed from the large number of patients (651
patients) included, in addition to the homogeneity of the
sample population. Results showed that the protocol
achieved the target blood glucose level faster than
Goldberg’s, in 3 hours (72.4% = nondiabetic) and (66.2% =
diabetic patients). Studer’s study  demonstrated
that under treatment conditions, nondiabetic patients
achieved a better glycaemic control with a lower
incidence of hypoglycaemic events than diabetic patients
and is consistent with a previous study . There were
only four observed cases of hypoglycaemia in Lecomte’s
study  and there were no associated adverse clinical
episodes in the work carried out by Goldberg’s group .
The effectiveness and safety of these protocols rests
with the fact that clinicians have pre-existing knowledge
of previous blood glucose values, current blood glucose
values and current insulin infusion rates, and this is
confirmed by the meta-analysis of the four studies with
controls [16-19], which showed that the percentage failure
of patients reaching target blood glucose levels
demonstrated a significant difference (P < 0.0005) from patients
failing to achieve target blood glucose levels in the
control group compared with patients treated by protocol
(Additional file 1: Table S2).
Owing to the stress of surgery and the use of
catecholamine and steroids during the perioperative period,
patient’s blood glucose values can fluctuate immediately
postoperatively . Therefore, a dynamic protocol that
regulates insulin dosage according to the relative change
of blood glucose concentration, rather than one absolute
blood glucose value is of great important in achieving
tight glycaemic control effectively without increasing the
risk of hypoglycaemia.
Intensive insulin management  is often required to
optimize glycaemic control but this can be associated
with insulin mismanagement, and severe hypoglycaemia
is possible . Hypoglycaemia, which requires
emergency medical assistance, is commonplace in patients
with longstanding insulin-treated type 1 and type 2
diabetes. Left untreated, severe hypoglycaemia can result in
morbidity and death. Severe hypoglycaemia  can be
prevented by utilizing appropriate medications and
medication regimens , and effective glucose
monitoring strategies  and technologies . This is
fully supported by our meta-analysis on the risk
of hypoglycaemia on the studies and the subgroup
(Additional file 2: Table S3) examined, in which the risk
of hypoglycaemia was significantly reduced compared
with control (P < 0.00001) between studies that used an
insulin infusion protocol.
Perioperative hyperglycaemia is associated with poor
outcomes in patients undergoing cardiac surgery.
Frequent postoperative hyperglycaemia in cardiac surgery
patients has led to the instigation of a quality
improvement insulin infusion sliding scale. A systematic review
was conducted, to determine whether a
protocoldirected insulin infusion sliding scale was as safe and
effective as conventional practitioner-directed insulin
infusion sliding scales. Seven research studies met the
inclusion criteria. Five studies compared their insulin
infusion protocols to the previous blood glucose
management practice. Overall glycaemic control showed
an improvement in all five studies. Of the seven
studies, four used controls and three had no controls.
Implementation of protocols led to blood glucose
concentrations being achieved more readily. Moreover, blood
glucose ranges were maintained for a longer time, without
any increased frequency of hyperglycaemia.
The protocol-directed insulin infusion sliding scale
is a safe and effective method.
Blood glucose control is improved when compared
with the conventional practitioner-directed insulin
infusion sliding scale.
This study supports the adoption of a
protocoldirected insulin infusion sliding scale as a standard
of care for post-cardiac surgery patients.
An effective protocol should be based on the
velocity of glycaemic changes and patient’s insulin
The current blood glucose level, previous blood
glucose levels and relative change of blood glucose
levels between two consecutive measurements, as
well as the patient’s insulin resistance status, are
clinically important and should be used as
parameters of care, instead of relying solely on the
latest blood glucose level itself to adjust insulin
Additional file 1: Table S2. Percentage failure to reach target blood
Additional file 2: Table S3. Risk of hypoglycaemia.
The authors have no competing interests.
Conception and design: MLH/GGA; Analysis and interpretation: MLH/GGA;
Drafting the manuscript for important intellectual content:MLH/AK/GGA. All
authors read and approved the final manuscript.
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