Medical and Medicine

Perioperative Serum Glucose Control in Patients Undergoing Coronary Artery Bypass Graft Surgery

Hyperglycemia is a condition that occurs frequently in patients during cardiac surgery. This condition can occur whether the patient has diabetes or not. Research has found that both intraoperative and postoperative glucose measurements can be important predictors of outcomes after cardiac surgery. Postoperative, but not intraoperative, glycemic variability has been found to have an effect on morbidity and mortality. The research that has been conducted to date is very inconsistent in its findings as to what factors are important and which ones are not. There have also been discrepancies on the idea of glucose control during surgery. These inconsistencies leave a lot of room for further research in this area in order to further pinpoint what factors are important and how each of these factors influences the outcomes of patients who undergo cardiac surgery.

Introduction

Hyperglycemia is a condition that frequently occurs in patients during cardiopulmonary bypass surgery1. This condition is not necessarily dependent on whether a person had diabetes prior to surgery. Severe hyperglycemia has often been associated with unfavorable outcomes after cardiac surgery. Several studies have been done on whether intraoperative and postoperative glucose concentrations have equal impact outcomes of surgery patients. A solid conclusion has yet to be determined 2. Historically Perioperative hyperglycemia has not been treated because it was not thought to be harmful.

Hyperglycemia is thought to be linked to adverse outcomes through both direct and indirect mechanisms. Hyperglycemia interferes with monocyte and neutrophil function, affects endothelial function and induces the expression of proinflamatory cytokines. These events are thought to be responsible for a directly negative effect of hyperglycemia, including the facilitation of wound infection or sepsis1.

Conventionally, diabetes mellitus (DM) has been associated with poor clinical outcomes after cardiac surgery. This has included a higher frequency of wound infections, ischemic events, neurological and renal complications, and mortality. The frequency of DM has greatly done up in developed countries, over the past decade. Knowledge of the patients’ diabetic status preoperatively has led to advances in Perioperative clinical management that has included active and continuous blood glucose control (BGC). This has lead to improved clinical outcomes4.

Materials/Methods

I conducted a literature search using the Google Scholar, EBSCO MegaFile and PubMed databases. The following search terms were used: perioperative glucose control, intraoperative glucose control, Perioperative glucose control CABG and CABG glucose control. I used only human studied that were published in English.

Three retrospective studies were selected for review. One was a random controlled study while one was a non-randomized study.

Results

. Prevention of hyperglycemia might not reduce Perioperative difficulties, and the risks and costs of intensive intraoperative glycemic management may outweigh the benefits. Research has shown that an association between intraoperative hyperglycemia and adverse outcomes based on observational studies does not prove causality. Because hyperglycemia can have negative effects such as reduced immunity, wound healing, and vascular function, the idea that normoglycemia be upheld during the relatively brief duration of cardiac surgery seems reasonable. Some experts feel that the degree of intraoperative hyperglycemia is thought to be merely a reflection of the severity of underlying stress. Others feel that simple, safe, and effective insulin infusion algorithms that are needed in order to achieve rigorous intraoperative glycemic control are missing. In order to look at this issue, Gandhi, et al., (2007), conducted a randomized, controlled trial in order to determine whether maintenance of near normoglycemia during cardiac surgery by using intraoperative intravenous insulin infusion reduced Perioperative death and morbidity.

The results of this study showed that when intensive intravenous intraoperative insulin therapy was used in a controlled setting, it preserved glucose concentrations close to normal during surgery without increasing the risk for hypoglycemia. These results contradicted previous observational studies that showed that intraoperative hyperglycemia strongly predicted unfavorable postoperative outcomes after adjustment for the effects of postoperative glucose levels. This study also showed that lowering glucose concentrations to near normal levels intra-operatively by intravenous insulin infusion did not decrease short-term death, morbidity, or length of stay in the ICU or hospital. On the other hand, the increased incidence of death and stroke in the intensive treatment group brought about a concern in regards to routine implementation of this intervention 1.

Over the last decade, a large amount of evidence has brought to light the advances in intraoperative and intensive care techniques for diabetes mellitus patients undergoing cardiac surgery with improved outcomes.

In this study postoperative blood glucose levels were looked examined 8,727 patients. Results showed that 7,457 (85.4%) had good, 905 (10.4%) had moderate, and 365 (4.2%) had poor BGC in the first 60 hours following surgery. Patients who had moderate or poor BGC were thought to be more likely to have had a history of congestive heart failure, hypertension, arrhythmia or renal failure. The researchers found that 48.2% of patients who were in the poor BGC group and 68.5% who were in the moderate group were nondiabetic. They did find though that moderate BGC and poor BGC were more prevalent among DM patients. Overall, the study found that the number of patients with insufficient BGC declined over time 4.

In a study done by Duncan, Abd-Elasyed, Maheshwari, Xu, Soltesz and Kock, (2010), an investigation was done in order to compare the ability of perioperative glucose concentrations and glycemic variability to predict adverse outcomes. Risk associated with diminishing increments of glucose concentrations, hypoglycemia and diabetic status was also looked at. The patient population of this study included 4,302 patients who had undergone cardiac surgery. The results of this study showed that patients with diabetes had poorer outcomes compared to those patients without diabetes. The occurrence of diabetes almost doubled the danger of mortality. On the other hand, no relationship was found between the presence of diabetes and the influence of hyperglycemia on outcomes. Patients who had diabetes, even though they were at increased risk for adverse outcomes because of having diabetes, were found to have the same risk as patients without diabetes in regards to the degree of hyperglycemia.

In a study done by Furnary, Wu and Bookin, (2004), The Portland Diabetic Project, looked at the adverse relationship between hyperglycemia and outcomes of cardiac surgical procedures in patients with diabetes and delineated the protective effects of intravenous insulin therapy in reducing these adverse outcomes. This was a 17-year prospective, nonrandomized, interventional study involving 4,864 patients who had diabetes and who had undergone an open-heart surgical procedure. They looked into the effects of hyperglycemia, and its resulting reduction by continuous intravenous insulin (CII) therapy. High blood glucose levels were found to be directly related to increasing rates of death, deep sternal wound infections (DSWI), length of stays (LOS), and overall costs. In a separate multivariate analysis that was conducted it was found that increasing hyperglycemia was an independent projector of increasing mortality.

In a study done by Doenst, Wijeysundera, Karkouti, Zechner, Maganti, Rae and Borger, (2005), the influence of hyperglycemia during cardiopulmonary bypass on perioperative morbidity and mortality in diabetic and nondiabetic patients was examined. Results showed that the overall mortality rate was 1.8%. High glucose intensity during cardiopulmonary bypass was found to be an independent forecaster of mortality in both diabetic and nondiabetic patients. It was found that a high glucose level during cardiopulmonary bypass was also an autonomous predictor of all major adverse events in both groups of patients. It was found that a high glucose level was not directly correlated to cardiopulmonary bypass. It has been determined that a high serum glucose level measured during cardiopulmonary bypass is an independent risk cause for both death and morbidity in diabetic patients and nondiabetic patients alike.

This study also ascertained that hyperglycemia can be linked with adverse postoperative outcomes with both diabetic and nondiabetic patients. These researchers have suggested that hyperglycemia is a sign of a state of insulin resistance that is often developed during surgical intervention and that this insulin resistance contributes to poor outcomes, rather than the hyperglycemia by itself. They speculated that the treatment of insulin resistance might improve outcomes in all patients undergoing cardiac surgery3.

Discussion

This research has shown that hyperglycemia can be associated with negative outcomes after cardiac surgery and that this relationship is there in both diabetic and nondiabetic patients. Furnary, et al., (2004), established a direct relationship between postoperative glucose levels and mortality in patients with DM5. Other research found that both intraoperative and postoperative glucose measurements are important predictors of outcomes after cardiac surgery. In addition, postoperative, but not intraoperative, glycemic variability has been found to have an independent effect on morbidity and mortality2. In the study done by Gandhi, et al., (2007), glucous-insuline-potasium infusions were initiated just before anesthetic induction and for 12 hours following surgery. Patients who received these infusions were shown to have substantially lower incidences of atrial fibrillation than did those patients who received the standard therapy. It was also found that this group had shorter times of postoperative care along with shorter hospital stays. Patients who were given these infusions also showed a survival improvement and had decreased incidents of repeated ischemia and wound infections for two years following surgery. Another group demonstrated that when insulin infusion was initiated in patients in the operating room before sternotomy and continued until the third postoperative day that there was improved glucose control. There was a 57% decrease in mortality rate, compared with control groups who were treated with subcutaneous insulin. Patients with diabetes have been shown to have worse outcomes compared to patients without diabetes. There have been no relationship was found between the presence of diabetes and the influence of hyperglycemia on outcomes. Patients who have diabetes, even though they are at increased risk for adverse outcomes because of having diabetes, have been found to have the same risk as patients without diabetes. Based upon these findings it would seem reasonable to say that that Perioperative serum glucose control for patients undergoing Coronary Artery Bypass surgery would be an encouraged best practice.

It has been found that strict glucose control is often difficult to achieve during cardiac procedures requiring cardiopulmonary bypass because of the stress of surgery. Administration of large amounts of insulin during surgery has been associated with an increased risk for postoperative hypoglycemia. Research has shown though, that glucose concentrations if maintained during surgery as close to normal as possible, by the use of carefully monitored intravenous insulation fusion procedure, does not increase the risk for hypoglycemia. Although it has been shown that glucose concentration in groups given insulin treatment during surgery were lower than those in conventional groups, postoperative complications were not any different1. It has also been found that a high glucose level during cardiopulmonary bypass is an autonomous predictor of all major adverse events in patients. It has been found that a high glucose level is not directly correlated to cardiopulmonary bypass. A high serum glucose level during cardiopulmonary bypass has been found to be an independent risk factor adverse outcome in diabetic patients and nondiabetic patients alike.

The findings of the study done by Ascione, Rogers, Rajakaruna and Angelini, (2008), found that insulin infusion practice during surgery was not effectual in maintaining tight blood sugar control in all patients regardless of their diabetic status. It is thought that the stress of cardiac surgery might bring about a borderline diabetic status causing a marked temporary or permanent imbalance in body sugar control leading to hyperglycemia. Because hyperglycemia has been linked with poor outcomes it is thought that insulin infusion protocol should be extended to 48 hours after surgery in all patients regardless of their diabetic status. These findings have been found to contradict these other studies.

Although the results of these studies are intriguing, there are two potentially confounding factors that make their interpretation difficult. Postoperative serum glucose levels in diabetic patients are thought to be an indication of the severity of their disease, which might be an indicator for more co-morbidities and greater insulin resistance. It is also thought that patients with poor outcome are more likely to receive more glycogenic drugs than patients with an uncomplicated course and will therefore most likely have higher postoperative glucose levels3.

Conclusion

Both patients with known diabetes and those without have been found to be at risk for complications following cardiac surgery. Intraoperative and postoperative glucose measurements have been shown to be important predictors of outcomes after cardiac surgery. Even though severe hyperglycemia has been associated with adverse patient outcomes, involvement to normalize glycemia has yielded conflicting results. Whether hyperglycemia is a risk factor for adverse outcomes or merely a marker for severity of illness has yet to be determined. It is unclear whether associated benefits on outcomes result from treatment of hyperglycemia vs. benefits related to insulin therapy. Because insulin is the only clinically effective therapy that is currently available, it has found to be difficult to separate the effects of insulin from those of normalizing blood glucose in hyperglycemic patients.

Some research has found that both intraoperative and postoperative glucose concentrations are important indicators of postoperative morbidity and mortality. Although severe perioperative hyperglycemia is associated with an increased risk of adverse outcomes, incremental decreases in mean glucose concentrations has not shown to consistently moderate the risk during the intraoperative period. Research has shown that mean intraoperative glucose concentrations closest to normoglycemia were not associated with a lower risk for adverse outcomes. Increased postoperative glycemic variability has been associated with increased risk for adverse outcomes. It is thought that beneficial effects on outcomes may come from a higher target range of intraoperative glucose concentrations and lower perioperative glycemic variability.

Currently there is no consensus on what the optimal management of intraoperative hyperglycemia in cardiac surgical patients because of a lack of evidence from randomized trials. Researchers are increasingly extrapolating evidence from studies that assess the role of strict postoperative glycemic controls in patients to advocate for intravenous insulin therapy. An association established between intraoperative hyperglycemia and adverse outcomes based on observational studies does not prove causality. Due to the fact that hyperglycemia can negatively affect immunity, wound healing and vascular function the concept that normoglycemia be maintained during the brief duration of cardiac surgery. On the other hand, the degree of intraoperative may merely be a factor of the underlying stress of the surgery itself.

Although the association between hyperglycemia and Perioperative Serum Glucose Control has been established and agreed upon by most experts, the amount and degree of control during surgery has yet to be established. It has been found that strict glucose control is often difficult to attain during cardiac procedures because of the stress of surgery. Administration of large amounts of insulin during surgery has been associated with an increased risk for postoperative hypoglycemia. Research has shown that glucose concentrations if maintained during surgery as close to normal as possible, by the use of carefully monitored intravenous insulation fusion procedure, does not increase the risk for hypoglycemia.

Obviously there are many factors that must be looked at both preoperatively and postoperatively in regards to hyperglycemia and adverse outcomes. The research that has been conducted to date is very inconsistent in its findings. Most experts agree on the fact that Perioperative serum glucose control is a positive thing that needs to be done during Coronary Artery Bypass surgery. What they don’t agree on is the best way to control glucose during surgery in order to produce the most optimal outcomes. The fact that there is discrepancy in what would be considered best practice; this would be an area in which further research would be needed. These inconsistencies leave a lot of room for further research in this area in order to further pinpoint what factors are important and how each of these factors influences the outcomes of patients who undergo cardiac surgery. Overall Perioperative Serum Glucose Control is a good practice as it has been shown to be effective in patient outcomes during surgery, regardless of whether the patient has diabetes before surgery or not.

References

1. Gandhi, Gunjan Y., Nuttall, Gregory A., Abel, Martin D., Mullany, Charles J., Schaff, Hartzell

V., O’Brien, Peter C., Johnson, Matthew G., Williams, Arthur R., Cutshall, Susanne M.,

Munday, Lisa M., Rizza, Robert A., and McMahon, M. Molly. Intensive Intraoperative

Insulin Therapy vs. Conventional Glucose Management during Cardiac Surgery.

Annals of Internal Medicine. 2007; 146(4), p. 233-243.

2. Duncan, Andra E., Abd-Elasyed, Alaa, Maheshwari, Ankit, Xu, Meng, Soltesz, Edward and Kock, Colleen G. Role of Intraoperative and Postoperative Blood Glucose

Concentrations in Predicting Outcomes after Cardiac Surgery. Anesthesiology. 2010;

112(4), p. 860-271.

3. Doenst, Torsten, Wijeysundera, Duminda, Karkouti, Keyvan, Zechner, Christopher, Maganti,

Manjula, Rae, Vivek and Borger, Michael A. Hyperglycemia during cardiopulmonary bypass is an independent risk factor for mortality in patients undergoing cardiac surgery. The Journal of Thoracic and Cardiovascular Surgery. 2005; 130(4)

1144.e1-1144.e8.

4.Ascione, R., Rogers, C.A., Rajakaruna, C. And Angelini, G.D. Inadequate Blood Glucose

Control is Associated with In-Hospital Mortality and Morbidity in Diabetic and Nondiabetic Patients Undergoing Cardiac Surgery. AHA Journal. 2008; 118, p. 113-123.

5. Furnary, Anthony P., Wu, YingXing and Bookin, Stephen O. Effect of Hyperglycemia

and Continuous Intravenous Insulin Infusions on Outcomes of Cardiac Surgical Procedures:

The Portland Diabetic Project. Endocrine Practice. 2004; 10, Suppl 2, p. 21-33.