Is tight intraoperative control of blood glucose indicated in cardiac surgical patients?

Reviewers: Christian Bohringer, MD; Hong Liu, MD
University of California Davis Health System
Sacramento, CA

Patients with diabetes mellitus who undergo cardiopulmonary bypass (CPB) surgery have increased perioperative morbidity and mortality, reduced long-term survival, and an increased incidence of recurrent angina. Peri-operative hyperglycemia and insulin resistance are common in patients undergoing CPB surgery even in those who have previously normal glucose homeostasis. Increased gluconeogenesis despite an abundant release of insulin is probably central to this disruption of glucoregulation. It has been suggested that tighter blood glucose control improves long-term outcome in patients with acute myocardial infarctions and in patients following CPB surgery, but the question of how tightly the blood glucose should be controlled is still controversial.

Tighter blood glucose control has been associated with improved patient outcome in two recent critical care unit studies.^1,2 Both studies were performed in a surgical ICU population with a large percentage of cardiac surgical patients. Van den Berghe¹ reported a reduction in mortality from 8% to 4.6% when blood glucose in the ICU was maintained below 110 mg/dl (6.1mmol/l) rather than the previous target of 215 mg/dl (12mmol/l). The greatest reduction in mortality was observed in patients with multi-organ failure and a proven septic focus. Patients in the tight control group were also less likely to develop blood stream infections, renal failure requiring dialysis and critical illness polyneuropathy. They were also less likely to require prolonged mechanical ventilation and had shorter ICU stays. Other studies have also confirmed lower renal failure and infection rates in cardiac surgical patients with tight glucose control^3,4 and improved neutrophil function has been suggested as the mechanism for the lower infection rates with insulin infusion.⁵ Stress induces hyperglycemia, and it has been associated with an increased risk of in hospital mortality after myocardial infarction or stroke.^6,7,8 It is not known whether it is the higher blood glucose level per se or the underlying stress response that is responsible for this association. Finney² found that it was the control of the blood glucose level rather than the absolute levels of exogenous insulin that accounted for the reduction in mortality. Patients who required more insulin to control their blood glucose had a higher ICU mortality.² This would suggest that it is the stress response rather than the glucose that is responsible for the observed outcomes.

Although these studies suggest that tight post-operative blood glucose control is beneficial, this is not as easy to achieve in the intraoperative and CPB setting and this therapeutic approach can increase the risk of inadvertent hypoglycemia. Even though Finney aimed for less tight control than Van den Berghe (145mg/dl (8.1 mmol/l) vs. 110 mg/dl (6.1mmol/l)), blood glucose levels in this trial were inherently difficult to control and many patients spent considerable periods of time with glucose levels outside the target range.² Previous investigations have also confirmed the difficulties associated with tighter control of blood glucose in patients undergoing CPB. Chaney et al in their group of 20 non-diabetic patients found that tight blood glucose control during CPB was not easily achievable and 40% needed treatment for hypoglycemia (60mg/dl) in the cardiac ICU afterwards.⁹ The reasons for the increased blood glucose levels during CPB include the stress response, insulin resistance during hypothermia,¹⁰ the absorption of exogenously administered insulin by the plastic in the extracorporeal circuit, ongoing glucose administration in the cardioplegia and steroids that are used in some centers in an attempt to ameliorate the inflammatory response to CPB.¹¹ More insulin is required to control blood glucose during CPB. The greater the degree of cooling during CPB, the greater will be the insulin resistance and the temptation to administer further doses of insulin. Once the body temperature has returned to normal, the insulin resistance disappears and there is an associated potential for developing profound hypoglycemia.

The effects of unrecognized hypoglycemia can be devastating. When Sakel induced hypoglycemic coma with insulin infusions in a misguided attempt to treat schizophrenia in the 1930's, he noted that the coma became irreversible if it lasted for more than 30 minutes.¹² Hypoglycemia is even more difficult to recognize during anesthesia because patient experiences none of the early warning signs of hypoglycemia (hunger, sweating, headache, irritation, lack of concentration, tremor, muscle weakness or visual disturbances). The task of preventing hypoglycemic brain damage during tight intraoperative glucose control protocols is therefore entirely up to the anesthesiologist. When tight control is desired, blood glucose may need to be checked as often as every 15 minutes and dextrose infusions need to be immediately available on standby to treat hypoglycemia. Dextrose should be administered when blood glucose falls below 60mg/dl (3.3mmol/l). In addition, tight intraoperative glucose control is also associated with a risk of hypokalemia. Since potassium is transported intracellularly along with the glucose and insulin, it is therefore prudent to check serum potassium concentrations frequently and replace as needed.

In summary, tight postoperative control of blood glucose has been associated with significant benefits. Tight intraoperative control of blood glucose may be indicated as well in cardiac surgical patients. But, if tight glucose control is attempted during the intraoperative period, frequent glucose and potassium monitoring is required and must be extended into the ICU and the recovery period because of the significant potential for catastrophic hypoglycemia.

References:

1. Van den Berghe G, Wouters P, Weekers F, et al. Intensive Insulin therapy in critically ill patients. N Engl J Med 2001; 345: 1359-1367
2. Finney SJ, Zekvaeld C , Elia A, et al: Glucose control and mortality in critically ill patients. JAMA 2003; 290: 2041-2047
3. Furnary A, Zerr K, Grunkemaier G et al. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999; 67: 352-360
4. Mangano C, Diamonstone L, Ramsey J et al. Renal dysfunction after myocardial revascularization: Risk factors, adverse outcomes and hospital resource utilization. Ann Intern Med 1998; 128: 194-203
5. Rassias A, Marrin C, Arruda J et al. Insulin infusion improves neutrophil function in diabetic cardiac surgery patients. Anesth Analg 1999;88: 1011-1016
6. Capes S , Hunt D , Malmberg K et al. Stress hyperglycemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000 ; 355: 773-778
7. Capes S, Hunt D, Malmberg K et al. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients. Stroke 2001; 32: 2426-2432
8. Furnary A, Wu Y, Bookin S. Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project. Endocr Pract 2004; 10: 31-33
9. Chaney M, Nikolov M, Blakeman, B et al. Attempting to maintain normoglycemia during cardiopulmonary bypass with insulin may initiate postoperative hypoglycemia. Anesth Analg 1999; 89: 1091-1095
10. Lehot J, Piriz H, Villard J et al. Glucose homeostasis. Comparison between hypothermic and normothermic cardiopulmonary bypass. Chest 1992; 102: 106-111
11. London M, Grunwald G, Shroyer A et al. Association of fast track cardiac management and low-dose to moderate-dose glucocorticoid administration with perioperative hyperglycemia. J Cardiothorac Vasc Anesth 2000; 14; 631-638
12. Sakel M. Schizophreniebehandlung mittels insulin-hyoglykaemie sowie hypoglykaemischen schocks. Wien Med. Wchnschr 1934; 84: 1211

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Table of Contents:

• President's Message
• Journal Supplement to Disappear


• PRO/CON: Routine intraoperative PLV has been shown to improve outcome in patients affected by ALI/ARDS
• Pro - N. Petrucci, MD, MSc
• Con - Andrew Maslow, MD


• Literature Reviews
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  • Coronary-artery revascularization before elective major vascular surgery
  • Forty years of clinical aprotinin use: A review of 124 hypersensitivity reactions
  • Cerebral monitoring with transcranial Doppler ultrasonography improves neurologic outcome during repairs of acute type A aortic dissection.


• Drug and Innovation Reviews
  • Is tight intraoperative control of blood glucose indicated in cardiac surgical patients?

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