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.