Cardiac Intensive Care
Safe and Effective Use of a Glycemic Control
Protocol for Neonates in a Cardiac ICU*
Camden L. Hebson, MD1; Nikhil K. Chanani, MD1; Mark R. Rigby, MD2; Michael J. Wolf, MD1;
Shriprasad R. Deshpande, MD1; Leticia M. Montegna, PharmD3; Kevin O. Maher, MD1
Objective: To investigate the safety and efficacy of a hyperglyce-
mia protocol in neonates with critical cardiac illness. Neonates
are often regarded as high risk for hypoglycemia while receiving
continuous insulin infusions and thus have been excluded from
some clinical trials.
Design: A retrospective review.
Setting: A pediatric cardiac ICU in a tertiary academic center.
Interventions: Neonates with critical cardiac illness who devel-
oped hyperglycemia were placed on an insulin-hyperglycemia
protocol at the attending physician’s discretion. Insulin infusions
were titrated based on frequent blood glucose monitoring.
Measurements: Critical illness hyperglycemia was defined as a blood
glucose less than 140 mg/dL. Hypoglycemia was defined as moderate
(≤ 60 mg/dL) or severe (≤ 40 mg/dL). Initiating blood glucose, lowest
blood glucose during insulin infusion, doses of insulin, duration of insu-
lin, and time to blood glucose greater than 140 mg/dL were evaluated.
Main Results: A total of 44 patients were placed on the proto-
col between January 2009 and October 2011. The majority of
H
yperglycemia during critical illness is associated with
increased morbidity and mortality, both in children
and adults (1–16). In adults, trials examining the effect
of tight glycemic control have produced conflicting results: some
have shown beneficial effects, whereas others have shown no
benefit or even potential for harm with concern for increased
prevalence of hypoglycemia (17–24). As a result of these trials, the
American Diabetes Association now recommends maintaining
a blood glucose (BG) range of 140–180 mg/dL for intensive care
*See also p. 328.
1
Division of Pediatric Cardiology, Department of Pediatrics, Emory Uni-
versity School of Medicine/Children’s Healthcare of Atlanta, Atlanta, GA.
2
Section of Pediatric Critical Care, Indiana University School of Medicine/
Riley Hospital for Children, Indianapolis, IN.
3
Pharmacy Department, Children’s Healthcare of Atlanta, Atlanta, Georgia.
Dr. Chanani receives funding from the National Institutes of Health (NIH).
The remaining authors have not disclosed any potential conflict of interest.
For information regarding this article, E-mail: chebson@emory.edu
Copyright © 2013 by the Society of Critical Care Medicine and the World
Federation of Pediatric Intensive and Critical Care Societies
DOI: 10.1097/PCC.0b013e31827200de
284 www.pccmjournal.org March 2013 • Volume 14 • Number 3
insulin infusions were initiated in the early postoperative period
(33 of 44, 75%). Moderate hypoglycemia occurred in two patients
(4.5%), with blood glucose levels of 49 and 53 mg/dL. No episodes
of severe hypoglycemia occurred. A total of 345 discrete blood
glucose levels were analyzed; two of these being greater than
60 mg/dL (0.58%). Mean blood glucose prior to starting insulin
was 252 ± 45 mg/dL and time until euglycemia was 6.1 ± 3.9 hours.
The mean duration of insulin infusion was 24.6 ± 38.7 hours, mean
peak dose was 0.10 ± 0.05 units/kg/hour, and mean insulin dose
was 0.06 ± 0.02 units/kg/hour. For postoperative patients, mean
time after bypass until onset of hyperglycemia was 2.2 ± 2.6 hours.
Conclusions: A glycemic control protocol can safely and effec-
tively be applied to neonates with critical cardiac disease. Neo-
nates with critical cardiac illness should be included in clinical
trials evaluating the benefits of glycemic control. (Pediatr Crit
Care Med 2013; 14:284–289)
Key Words: congenital; critical illness; heart defects;
hyperglycemia; infant; insulin; intensive care; newborn
patients (25). The first pediatric glycemic control outcome trial was
conducted by Vlasselaers et al (21), who demonstrated improved
morbidity and reduced mortality in patients who received insulin
infusions targeting BG concentrations to age-adjusted normal
values. There was, however, a significantly increased risk of severe
hypoglycemia in the intensive BG control group. As a result of
these studies and others, the National Institutes of Health (NIH)
have currently excluded neonates from some large randomized
controlled trials regarding insulin infusions in pediatric critical
care units (due to the concern that neonates may be particularly
vulnerable to hypoglycemia). The purpose of this article is to
review this institution’s experience with use of a glycemic control
protocol in neonates in the cardiac ICU (CICU).
MATERIALS AND METHODS
A retrospective chart review of all neonates (age < 30 days)
admitted to our CICU, from January 2009 to October 2011,
was completed. Of the 392 neonates admitted during the study
period, 44 (11%) were placed on an insulin infusion. Insulin
was administered via a previously published, standardized,

pediatric-specific protocol developed at our institution (15, 16,
26). The protocol is principally managed by nursing and begun
on patients who meet certain preidentified hyperglycemia risk
factors (mechanical ventilation, inotropic support, etc). Once
initiated, patients are screened for hyperglycemia at least every
12 hours and insulin is initiated once hyperglycemia criteria
are met. For infants < 1 month of age, protocol initiation was
at the discretion of the attending physician. Blood samples are
predominantly collected from either arterial or central venous
catheters and then determined at bedside using portable
i-STAT handheld devices (Abbott Laboratories, Abbott Park,
IL). Further details of our glycemic control protocol are pre-
sented in Figure 1. This retrospective review was performed
with approval of the Institutional Review Board at Children’s
Healthcare of Atlanta with waiver of informed consent.
The primary outcome of interest for this study was hypo-
glycemia. Moderate hypoglycemia was defined as BG ≤ 60 mg/
dL, whereas severe hypoglycemia was defined as ≤ 40 mg/dL.
Lowest BG value for each patient during the insulin infusion
was determined to evaluate this outcome. Hyperglycemia was
defined as a BG level > 140 mg/dL for two consecutive mea-
surements, at least 1 hour apart. Salient preoperative, operative
(if applicable), and postoperative characteristics were collected.
Each patient’s BG value at the initiation of the glycemic pro-
tocol, average and peak doses of insulin required, duration of
Figure 1.  Emory/Children's Healthcare of Atlanta pediatric critical illness
hyperglycemia protocol (< 5 kg).
Pediatric Critical Care Medicine www.pccmjournal.org 285
Cardiac Intensive Care
insulin drip, and time to BG < 140 mg/dL (euglycemia) were
determined. Finally, we compared time to euglycemia, between
the study cohort and a relatively matched group of neonates
who received intermittent insulin doses, to further evaluate the
efficacy of the insulin infusion protocol. The intermittent insu-
lin group of neonates was treated over the same time period
(January 2009 to October 2011) as the study group, but received
intermittent doses of insulin at the discretion of the attending
physician. Data are presented as mean values with standard
deviations, which were derived using Microsoft Excel 2007.
Comparisons were made using Student t test and chi-square
test for continuous variables and categorical variables, respec-
tively. Significant difference was defined as p value < 0.05.
RESULTS
Of the 392 patients admitted to the CICU during the study
period, 44 (11%) were placed on the glycemic control proto-
col. Per institutional protocol, all neonates undergoing cardio-
pulmonary bypass received intravenous methylprednisolone
10 mg/kg preoperatively and then 30 mg/kg in the bypass
circuit prime. Preoperative, operative, and postoperative char-
acteristics of the study population are presented in Table 1.
Among the 44 study patients, 345 discrete BG values were
obtained. The mean BG level for initiation of the glycemic pro-
tocol was 252 mg/dL with a range of 177–402 mg/dL. Two (4.5%)
patients had a single episode of moderate hypoglycemia (0.58%
of BG values). The first patient had a low BG of 49 mg/dL. The
low BG value was preceded over the previous 2 hours by BG val-
ues of 101 and 62 mg/dL, was appropriately treated per the gly-
cemic control protocol, and corrected to 79 mg/dL within 1 hour
by turning off the insulin infusion and increasing the patient’s
glucose infusion rate from 0.9 to 2 mg/kg/minute. The second
patient had a low BG of 53 mg/dL. The patient was appropriately
treated with insulin over the previous 2 hours for BG values of
221 and 102 mg/dL. The low value was corrected within 1 hour
to 110 mg/dL by stopping insulin and increasing the glucose infu-
sion rate from 2.6 to 4.3 mg/kg/minute. There were no episodes
of severe hypoglycemia and no documented sequelae (seizures,
apnea, temperature instability, change in ventilatory, or inotro-
pic support) from either episode of transient moderate hypogly-
cemia. The mean lowest BG value for the study population was
90 ± 28 mg/dL. Study outcomes are otherwise listed in Table 2
and individual BG values over time for each study patient, along
with delineation of the 25th, 50th, and 75th percentile values, are
presented in Figure 2.
Table 3 summarizes the comparison between hyperglyce-
mic neonates treated with an insulin drip and those treated
with intermittent insulin doses.
DISCUSSION
Hyperglycemia is an exceptionally common occurrence dur-
ing critical illness. Although initially considered a marker of
severe illness (27, 28), it is now regarded as detrimental to
recovery. Hyperglycemia manifests during critical illness due
to counterregulatory hormone-induced increases in glucose
Hebson et al

Table 1.  Baseline Characteristics of the Table 2.  Study Outcomes

Study Population Patients with moderate hypoglycemiaa during 2 (4.5)
Age (mean ± sd, days) 9.2 ± 8.5 insulin infusion (n, %)

Weight (mean ± sd, kg) 3.2 ± 0.8
Cardiopulmonary bypass operation (n, %) 38 (86)
Cardiopulmonary bypass time (mean ± sd, 136.4 ± 51.4
min)
Aortic cross clamp operation (n, %) 40 (91)
Cross clamp time (mean ± sd, min) 61.6 ± 30.2
Mechanical ventilation time (mean ± sd, hr) 168.7 ± 176.1
ICU length of stay (mean ± sd, hr) 320.5 ± 427.4
Genetic syndromea (n, %) 7 (16)
ICU deathb (n, %) 8 (18)
Anatomic diagnosis (n = 44)
Total anomalous pulmonary venous return 12 (27)
(n, %)
Hypoplastic left heart syndrome (n, %) 7 (16)
Coarctation of the aorta (n, %) 5 (11)
Transposition of the great arteries (n, %) 4 (9)
Complete atrioventricular canal (n, %) 2 (4.5)
Tetralogy of Fallot with absent pulmonary 2 (4.5)
valve (n, %)
Double outlet right ventricle (n, %) 2 (4.5)
Interrupted aortic arch (n, %) 2 (4.5)
2 (4.5)
Heterotaxy, single ventricle variant (n, %)
Other (n, %) 6 (14)
a
Genetic syndromes included DiGeorge, CHARGE, Cat-eye, and Down
syndromes.
b
Death prior to discharge from the cardiac ICU.
production, peripheral insulin resistance, and endogenous
insulin deficiency (29). Inflammatory states, such as post–
cardiopulmonary bypass, potentiate these mechanisms. Once
hyperglycemia is established, deleterious effects occur at the
cellular level, including mitochondrial dysfunction (30), ener-
vated immune response (31), and endothelial dysfunction (32).
Although exogenous insulin administration has been shown to
attenuate these processes and normalize BG levels (33–36), the
trade-off of hypoglycemia has been reported, occurring in 5%
to 29% of patients (17–19, 21–24). The deleterious effects of
hypoglycemia are well-described, including short-term cellu-
lar dysfunction and long-term neurocognitive delay (if hypo-
glycemia is sustained). Neonates are at particular risk for harm
due to limited glycogen stores, immature counterregulatory
responses, and increased glucose demand (37). This problem
is intensified following cardiac surgery, when patients are fluid
restricted, which can limit glucose infusion rates. For these
reasons and others, neonates have been excluded from some
Prevalence of moderate hypoglycemia over 2 (0.58)
345 lab draws (n, %)
Patients with severe hypoglycemiab during 0 (0%)
insulin infusion
Blood glucose prior to starting insulin 252 ± 45
(mean ± sd, mg/dL)
Mean lowest blood glucose during insulin 90 ± 28
infusion (mean ± sd, mg/dL)
Time on insulin until euglycemiac achieved 6.1 ± 3.9
(mean ± sd, hr)
Duration of insulin infusion (mean ± sd, hr) 24.6 ± 38.7
Peak dose of insulin during infusion 0.10 ± 0.05
(mean ± sd, units/kg/hr)
Mean dose of insulin during infusion 0.06 ± 0.02
(Mean ± sd, units/kg/hr)
Percentage of insulin infusions begun in 33 (75)
the early postoperative period (n, %)
Time from bypass (if used) until onset of 2.2 ± 2.6
hyperglycemia (Mean ± sd, hr)
a
Moderate hypoglycemia = blood glucose ≤ 60 mg/dL.
b
Severe hypoglycemia = blood glucose ≤ 40 mg/dL.
c
Euglycemia = blood glucose < 140 mg/dL.
prospective trials of the efficacy of insulin infusions in pedi-
atric critical care patients. Our experience, however, has been
that a well-crafted glycemic control protocol can be safely used
in this patient population with critical cardiac illness.
The prevalence of moderate hypoglycemia in our study
was 4.5%. No instances of severe hypoglycemia occurred and
the mean lowest BG value for the study group was 90 ± 28 mg/
dL—moderate hypoglycemia occurred outside of the stan-
dard deviation range. This compares favorably with pub-
lished prospective trials. Beardsall et al (17) reported a 29%
occurrence rate in their treatment group of low-birth-weight
infants; however, the authors treated all infants regardless of
BG level as opposed to our strategy of only treating neonates
who were hyperglycemic. Our study represents a five-fold
decrease in hypoglycemia compared with the largest pediat-
ric prospective trial to date (19). Undoubtedly, this reflects a
more lenient target BG range, as Vlasselaers et al targeted a
range of 50–80 mg/dL, whereas our protocol aims to maintain
BG levels between 80 and 140 mg/dL. Although more tolerant,
it is important to point out that our target range is lower than
the latest recommendations made by the American Diabetes
Association in adults (25). The frequency of BG checks likely
also contributed to the decreased prevalence of hypoglycemia
we report. In our protocol, BG levels are checked at least every
1–2 hours compared with every 1–4 hours in the study by
Vlasselaers et al. As new BG monitoring systems are imple-
mented, further improvement can be expected (38, 39).

286 www.pccmjournal.org March 2013 • Volume 14 • Number 3


Figure 2.  Individual glucose changes while on an insulin infusion (n = 44).
Balance between safety and efficacy is paramount in any
glycemic control protocol design. In this study, the average
time period to BG < 140 mg/dL was 6.1 ± 3.9 hours from time
of initiation. This represents a reasonable time period despite
starting on average at a BG value of 252 ± 45 mg/dL. Higher
BG values at initiation of insulin infusions in this study are
likely the result of physicians’ reluctance to use insulin in
neonates. Following completion of this study, there has been
uniform adoption of this protocol to reduce care variabil-
ity at our institution. Although the higher starting BG values
could be interpreted as confounding the safety results of this
study, because the buffer above hypoglycemia was high, there
is evidence to the contrary. As illustrated in Figure 2, BG val-
ues gradually declined toward euglycemia rather than abruptly
decreasing in the majority of patients. Of course, further
study is needed to prove that similar gradual declining slopes
would occur regardless of the BG level at which the protocol
is started. Finally, compared with a relatively matched group
of neonates who received intermittent insulin, the continuous
insulin group achieved euglycemia in a significantly shorter
time period. Although not a true comparison, as neither form
of insulin was administered at the time with the sole intent
being fastest correction of hyperglycemia, the result remains
favorable compared with another potential treatment option.
The average duration of insulin infusion in our study was quite
high. Some explanation comes from the protocol itself, which
requires at least 6 hours of BG < 140 mg/dL on an insulin dose
≤ 0.02 units/kg/hour prior to discontinuation. Six outlier patients
provide further insight: they received insulin for 188, 118, 112,
111, 91, and 64 hours, respectively. Exclusion of these patients
changes the cohort’s mean duration to 10.5 ± 7.1 hours, which is
more in line with our experience. Required doses of insulin were
also relatively high; however, Beardsall et al and Vlasselaers et al
reported similar doses (17, 21). The likely explanation in this case
Pediatric Critical Care Medicine www.pccmjournal.org 287
Cardiac Intensive Care
is the elevated mean starting BG level, cited earlier, combined
with the protocol design, which uses a cut-off of 140 mg/dL as
a stimulus to more aggressively up-titrate insulin levels until
euglycemia is achieved. Regardless, as demonstrated in Fig. 2,
the higher required insulin doses gradually decreased mean BG
levels toward euglycemia, and did so in neonates with theoreti-
cally less counterregulatory reserve. A final outcome to discuss is
that the majority of the insulin infusions (75%) were begun in
the immediate postoperative period. Cardiopulmonary bypass
stimulates a systemic inflammatory response and the cytokine
“storm” that follows leads to peripheral insulin resistance and
pancreatic beta-cell dysfunction, among other mechanisms (39).
Systemic steroids are also thought to lead to insulin resistance
and beta-cell dysfunction. Therefore, although it is not surpris-
ing that BG levels were elevated during this time period, readers
should consider that the distinct mechanism of hyperglycemia
that our patients represent might limit more generalized appli-
cability to other patient populations.
The limitations to this study include those inherent to any
retrospective review. Specific limitations include the possibil-
ity that hypoglycemia was missed in between designated BG
checks. Although the lack of lability over time in BG values
and low prevalence of hypoglycemia make this less likely, use of
continuous glucose monitors in future studies would address
this concern. Secondly, the conclusion that no harm came from
the two discrete episodes of moderate hypoglycemia found
during this study cannot be made with complete conviction
without long-term follow-up, including neurocognitive assess-
ments. Finally, this population was primarily a postoperative
cohort at the highest risk for hyperglycemia. Extending this
work to neonates being treated for sepsis or other noncardiac
critical illness may manifest different glucose patterns, as these
patients’ stimuli for hyperglycemia would be different.
A well-crafted pediatric-specific glycemic control protocol
can safely and effectively be applied to neonates with critical
cardiac illness and hyperglycemia. Inclusion of such neonates
in randomized trials is necessary and appropriate in order to
definitively evaluate the benefits of such protocols on clinical
outcomes.
REFERENCES
1. Finney SJ, Zekveld C, Elia A, et al: Glucose control and mortality in
critically ill patients. JAMA 2003; 290:2041–2047
2. Krinsley JS: Effect of an intensive glucose management protocol
on the mortality of critically ill adult patients. Mayo Clin Proc 2004;
79:992–1000
3. Hermans G, Wilmer A, Meersseman W, et al: Impact of intensive
insulin therapy on neuromuscular complications and ventilator depen-
dency in the medical intensive care unit. Am J Respir Crit Care Med
2007; 175:480–489
4. Falciglia M: Causes and consequences of hyperglycemia in critical
illness. Curr Opin Clin Nutr Metab Care 2007; 10:498–503
5. Laird AM, Miller PR, Kilgo PD, et al: Relationship of early hyperglyce-
mia to mortality in trauma patients. J Trauma 2004; 56:1058–1062
6. Capes SE, Hunt D, Malmberg K, et al: Stress hyperglycaemia
and increased risk of death after myocardial infarction in patients
with and without diabetes: A systematic overview. Lancet 2000;
355:773–778
Hebson et al

Table 3.  Comparison of Cardiac ICU Neonates Treated With Continuous vs. Intermittent
Insulin due to Hyperglycemia
Insulin Drip Intermittent
(n = 44) Insulin (n = 32) p
Age (mean ± sd, days) 9.2 ± 8.5 6.6 ± 4.4 0.12
Weight (mean ± sd, kg) 3.2 ± 0.8 2.9 ± 0.7 0.09
Cardiopulmonary bypass (n, %) 38 (86%) 28 (88%) 0.9
Aortic cross clamp operation (n, %) 40 (91%) 30 (94%) 0.69
ICU length of stay (mean ± sd, hr) 320.5 ± 427.4 320.5 ± 230.6 0.99
ICU death (n, %) 8 (18%) 8 (25%) 0.49
Blood glucose prior to starting insulin (mean ± sd, mg/dL) 252 ± 45 243 ± 67 0.49
Administration begun in the early postoperative period (n, %) 33 (75%) 20 (63%) 0.26
Average number of insulin doses (mean ± sd) N/A 1.9 ± 1.4 N/A
Average dose of insulin (mean ± sd, units/kg) N/A 0.11 ± 0.02 N/A
Prevalence of moderate hypoglycemia during insulin
a
2 (4.5%) 1 (3.1%) 0.81
administration (n = patients, %)
Time on insulin until euglycemiab achieved (mean ± sd, hr) 6.1 ± 3.9 8.6 ± 4.1 0.01
N/A = not applicable.
a
Moderate hypoglycemia = blood glucose ≤ 60 mg/dL.
b
Euglycemia = blood glucose < 140 mg/dL. Time started at initiation of insulin drip vs. first dose of intermittent insulin given.

7. Falcao G, Ulate K, Kouzekanani K, et al: Impact of postoperative
hyperglycemia following surgical repair of congenital cardiac defects.
Pediatr Cardiol 2008; 29:628–636
8. Faustino EV, Apkon M: Persistent hyperglycemia in critically ill chil-
dren. J Pediatr 2005; 146:30–34
9. Piper HG, Alexander JL, Shukla A, et al: Real-time continuous glucose
monitoring in pediatric patients during and after cardiac surgery. Pedi-
atrics 2006; 118:1176–1184
10. Wintergerst KA, Buckingham B, Gandrud L, et al: Association of
hypoglycemia, hyperglycemia, and glucose variability with morbid-
ity and death in the pediatric intensive care unit. Pediatrics 2006;
118:173–179
11. Srinivasan V, Spinella PC, Drott HR, et al: Association of timing, dura-
tion, and intensity of hyperglycemia with intensive care unit mortality
in critically ill children. Pediatr Crit Care Med 2004; 5:329–336
12. Branco RG, Garcia PC, Piva JP, et al: Glucose level and risk of mor-
tality in pediatric septic shock. Pediatr Crit Care Med 2005; 6:470–
472
13. Klein GW, Hojsak JM, Schmeidler J, et al: Hyperglycemia and outcome
in the pediatric intensive care unit. J Pediatr 2008; 153:379–384
14. Yung M, Wilkins B, Norton L, et al; Paediatric Study Group; Australian
and New Zealand Intensive Care Society: Glucose control, organ fail-
ure, and mortality in pediatric intensive care. Pediatr Crit Care Med
2008; 9:147–152
15. Preissig CM, Rigby MR, Maher KO: Glycemic control for post-
operative pediatric cardiac patients. Pediatr Cardiol 2009;
30:1098–1104
16. Preissig CM, Rigby MR: Pediatric critical illness hyperglycemia: Risk
factors associated with development and severity of hyperglycemia in
critically ill children. J Pediatr 2009; 155:734–739
17. Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, et al: Early insu-
lin therapy in very-low-birth-weight infants. N Engl J Med 2008;
359:1873–1884
18. van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin ther-
apy in critically ill patients. N Engl J Med 2001; 345:1359–1367
19. Van den Berghe G, Wilmer A, Hermans G, et al: Intensive insulin
therapy in the medical ICU. N Engl J Med 2006; 354:449–461
20. Van den Berghe G, Wilmer A, Milants I, et al: Intensive insulin therapy
in mixed medical/surgical intensive care units: Benefit versus harm.
Diabetes 2006; 55:3151–3159
21. Vlasselaers D, Milants I, Desmet L, et al: Intensive insulin therapy for
patients in paediatric intensive care: A prospective, randomised con-
trolled study. Lancet 2009; 373:547–556
22. Finfer S, Chittock DR, Su SY, et al: Intensive versus conven-
tional glucose control in critically ill patients. N Engl J Med 2009;
360(13):1283–1297
23. Brunkhorst FM, Engel C, Bloos F, et al; German Competence Net-
work Sepsis (SepNet): Intensive insulin therapy and pentastarch
resuscitation in severe sepsis. N Engl J Med 2008; 358:125–139
24. Preiser JC, Devos P, Ruiz-Santana S, et al: A prospective randomised
multi-centre controlled trial on tight glucose control by intensive insu-
lin therapy in adult intensive care units: The Glucontrol study. Inten-
sive Care Med 2009; 35:1738–1748
25. Moghissi ES, Korytkowski MT, DiNardo M, et al; American Associa-
tion of Clinical Endocrinologists; American Diabetes Association:
American Association of Clinical Endocrinologists and American Dia-
betes Association consensus statement on inpatient glycemic con-
trol. Diabetes Care 2009; 32:1119–1131
26. Preissig CM, Hansen I, Roerig PL, et al: A protocolized approach to
identify and manage hyperglycemia in a pediatric critical care unit.
Pediatr Crit Care Med 2008; 9:581–588
27. Doenst T, Bothe W, Beyersdorf F: Therapy with insulin in cardiac sur-
gery: Controversies and possible solutions. Ann Thorac Surg 2003;
75:S721–S728
28. Taegtmeyer H: Energy metabolism of the heart: From basic concepts
to clinical applications. Curr Probl Cardiol 1994; 19:59–113
29. Preissig CM, Rigby MR: Hyperglycaemia results from beta-cell dys-
function in critically ill children with respiratory and cardiovascular fail-
ure: A prospective observational study. Crit Care 2009; 13:R27
30. Vanhorebeek I, Ellger B, De Vos R, et al: Tissue-specific glucose tox-
icity induces mitochondrial damage in a burn injury model of critical
illness. Crit Care Med 2009; 37:1355–1364
31. Perner A, Nielsen SE, Rask-Madsen J: High glucose impairs superox-
ide production from isolated blood neutrophils. Intensive Care Med
2003; 29:642–645

288 www.pccmjournal.org March 2013 • Volume 14 • Number 3


32. Langouche L, Vanhorebeek I, Vlasselaers D, et al: Intensive insulin
therapy protects the endothelium of critically ill patients. J Clin Invest
2005; 115:2277–2286
33. Vanhorebeek I, De Vos R, Mesotten D, et al: Protection of hepa-
tocyte mitochondrial ultrastructure and function by strict blood
glucose control with insulin in critically ill patients. Lancet 2005;
365:53–59
34. Furnary AP, Zerr KJ, Grunkemeier GL, et al: Continuous intravenous
insulin infusion reduces the incidence of deep sternal wound infec-
tion in diabetic patients after cardiac surgical procedures. Ann Thorac
Surg 1999; 67:352–60; discussion 360
35. Hansen TK, Thiel S, Wouters PJ, et al: Intensive insulin therapy exerts
antiinflammatory effects in critically ill patients and counteracts the
Pediatric Critical Care Medicine www.pccmjournal.org 289
Cardiac Intensive Care
adverse effect of low mannose-binding lectin levels. J Clin Endocrinol
Metab 2003; 88:1082–1088
36. Leffler M, Hrach T, Stuerzl M, et al: Insulin attenuates apoptosis and
exerts anti-inflammatory effects in endotoxemic human macrophages.
J Surg Res 2007; 143:398–406
37. Hawdon JM, Weddell A, Aynsley-Green A, et al: Hormonal and meta-
bolic response to hypoglycaemia in small for gestational age infants.
Arch Dis Child 1993; 68(3 Spec No):269–273
38. Steil GM, Langer M, Jaeger K, et al: Value of continuous glucose
monitoring for minimizing severe hypoglycemia during tight glycemic
control. Pediatr Crit Care Med 2011; 12:643–648
39. Bridges BC, Preissig CM, Maher KO, et al: Continuous glucose monitors
prove highly accurate in critically ill children. Crit Care 2010; 14:R176