Discussion
This study hypothesized that stress hyperglycemia associates with tissue
perfusion. This stress response may cause reduced tissue perfusion
parameters and may differ in non-diabetic patients and in patients with
non-insulin-dependent diabetes mellitus undergoing cardiac surgery. The
stress-induced hyperglycemic response during cardiac surgery was more
severe in noDM patients than in patients with NIDDM (1.14 & 0.879).
When focusing on the O2ER parameter in terms of tissue
oxygenation, NIDDM patients had 1.22 times higher and significant
O2ER values than NoDM patients. However, blood glucose
values and O2ER parameters had no effect on each other,
and/or no correlation was found between them.
Hyperglycemia is common in cardiac surgery and seen as high as 60-80%
of patients.8,14 Hyperglycemia occurs as a result of
decreased insulin production caused by pancreatic β cell insufficiency,
or insulin resistance. In the absence of autoimmune diabetes, transient
disturbances in pancreatic cell secretion during CPB were found to be
associated with hypothermia.15 However, the causes of
insulin resistance are the secretion of catecholamines and cortisone
against effects such as systemic inflammatory response syndrome,
hemodilution, systemic heparinization together with CPB (surgical
stress).5 The severity of the hyperglycemic response
increases with the intensity of the stress, so in cardiac surgery,
inflammation initially caused by anesthesia and surgery peaks together
with CPB and hypothermia.16 In our study, blood
glucose in the NoDM group which stress hyperglycemia ratio was found
78% reached its highest values at T2 and T3 periods, that is, when the
effects of CPB and hypothermia effects were strongest. In the NIDDM
group, blood glucose levels were above 140mg/dl from the beginning, and
also peaked during T2 and T3 periods, similar to the NoDM group. In
accordance with our clinical protocol, if blood glucose rises above
180mg/dl in the intraoperative period, continuous insulin infusion is
started. A randomized controlled study of 400 diabetic and non-diabetic
surgical patients comparing the two groups who received a continuous
infusion of insulin to keep the intraoperative glucose level between
80-100 mg/dL and the glucose target kept below 200 mg/dL did not report
any improvement in clinical outcome or
complications.17 In a meta-analysis including the
results of 706 cardiac surgery patients, it was reported that strict
intraoperative glycemic control decreased infection rate but not
mortality compared to conventional therapy.18 In
another coronary surgery patient group, when a blood glucose target of
90-120 mg / dL and 121-180 mg/dL was achieved, no difference was
observed in deep sternum wound infection, pneumonia, perioperative renal
failure, or mortality.19 Similarly, other studies
targeting the same glucose values did not report any difference between
the groups in terms of perioperative complications, length of stay in
hospital, and mortality.20,21 Although our study
population is smaller compared to these studies, we would like to state
that in our results, no difference was observed between non-diabetic and
NIDDM cardiac surgery patients in terms of postoperative complications
and mortality. As the surgery progressed, the rate of increase in blood
glucose observed in the NoDM group was higher than in the NIDDM group.
Although the mechanism is not fully known, all these studies show that
NIDDM provides a tolerance to stress-induced hyperglycemia, and an
approach that does not require tighter control can be preferred for
glycemic control with NIDDM.22
In general, global body oxygen delivery in anesthesia practice is
mathematically formulated by DO2, that is the product of
cardiac output and arterial oxygen content. Although medical
physiological facts often do not agree with this simple mathematical
calculation, interpretation can be made about tissue oxygenation by
evaluating many other parameters such as O2ER,
ScvO2, lactate, systemic vascular resistance (SVR) and
hemoglobin. It has been stated that global tissue hypoperfusion detected
with SvO2 and lactate is common in non-diabetic coronary
artery surgery patients, in addition high blood glucose level is not
suitable for use as a perioperative marker for global tissue
hypoperfusion.23 On the other hand, in another study,
it was suggested that patients with diabetes mellitus who underwent
cardiac surgery had impairments in cerebral oxygen saturation, possibly
due to microcirculatory disorders, and SvO2 measurement
did not reflect this deficiency.24 It is known that
hyperlactatemia seen in cardiac surgery does not always indicate an
anaerobic condition and/or a lack of tissue oxygen delivery, a condition
called type B hyperlactatemia.25,26 Conversely, it has
been suggested that reduced increase in lactate levels in the presence
of hyperglycemia may be a result of decreased activation of the
glycolytic pathway in patients with diabetes mellitus compared to
patients with NoDM.27 In our study, the lactate values
were around 2-3 mmol/L in both groups, which was quite acceptable during
cardiac surgery and the ScvO2 value was around 70% and
there was no clinical significance between the groups. No difference was
found between non-diabetic and NIDDM patients in terms of other
parameters such as hemoglobin, MAP, SVR and blood product transfusion,
but a significant difference emerged when the O2ER
parameter was examined. Accordingly, O2ER values in both
groups were above the normal value of 25%, and in addition, NIDDM
patients had significantly higher O2ER values. The
situations encountered with high O2ER are as follows:
inadequate oxygen delivery such as hypoxia, anemia, circulatory failure;
increased oxygen consumption such as increased muscle activity,
exercise, shivering, seizures, and inflammation; increased metabolic
rate such as hyperthermia, hyperthyroidism, catecholamine excess and
massive injury; abnormal circulation, such as cyanotic shunt,
arterio-venous malformation. In our study, the reason for the relatively
high O2ER from the beginning of the operation in
anesthetized patients may be because of inflammation, and/or increased
catecholamine due to the fear of surgery, as the surgery progresses,
many other factors such as hemoglobin decrease due to hemodilution,
hypothermia, nonpulsatile flow come into play and the severity of
inflammation increases. The critical DO2 in humans is
the maximum O2ER (O2ER 0.6-0.8) at ∼4ml
kg-1 min-1, and at this stage
VO2 is said to be supply dependent. If
DO2 continues to fall further below its critical value,
anaerobic metabolism and type A hyperlactataemia occur due to the
imbalance between ATP supply and demand. Although lactate values were
slightly higher and ScvO2 values were slightly lower in
the NIDDM group in our study, considering the fact that
O2ER reflects the total outcome of small changes in all
these parameters, we can emphasize the conclusion that NIDDM patients
undergoing cardiac surgery have greater tissue oxygen demand/supply
imbalance compared to NoDM patients. In our study, this tissue
oxygenation defect in NIDDM patients was not found to be directly
correlated with blood glucose levels. Perhaps, even if the disease is
under control, the negative effects of diabetes on all systems have
accumulated and led to such a result. Studies with more patients will
shed light on the subject.
Limitations of this study; while this theoretical understanding
underpins the physiology of oxygen in the critically ill patient,
empirical evidence to support them is limited and the concepts remain
controversial. Even if global oxygen supply and consumption appears to
be normal, it does not exclude the presence of pathological oxygen
supply/demand at the regional or local level. The small number of our
patients is another limitation as noted earlier. And it would be more
valuable if we had chance to measure cortisol levels to determine
catabolic stress.
This research did not receive any specific grants from funding agencies
in the public, commercial, or not-for-profit sectors.