Drs. Carvalho and Schricker ask for several details on the surgical interventions pertaining to the applicability of study findings to other settings rather than to the validity of results. It is important to realize that the degree of intraoperative glycemic control was the only difference in study intervention between the 2 groups. The beauty of randomization with allocation concealment is that all known and unknown prognostic variables should be equally distributed between the 2 study groups. Specific surgical details can be provided by personal communication but are beyond the scope of our response.

Although we appreciate the concerns of Drs. Assaly and Habib, we did not use etomidate for induction of anesthesia in our study patients. We chose the study outcomes not only because of clinical relevance, but also because other studies showed that glycemic control, insulin use, or both affected death (1, 2), stroke (3), prolonged mechanical ventilation (1, 2, 4), acute renal failure (2, 4), sternal wound infections (2), atrial fibrillation (2), and heart block requiring pacing (2).

We never claimed that normoglycemia was achieved during cardiac surgery. We were able to achieve as strict glucose control as was safely feasible by monitoring glucose levels every 30 minutes in the operating room (intensive by most standards). A hyperinsulinemic, normoglycemic clamp can achieve normoglycemia (5), but measurement of glucose concentration every 5 minutes with constant titrating of dextrose levels to clamp glucose levels at goal would not be practically feasible outside of a study protocol. Although a more aggressive insulin infusion protocol may have further decreased intraoperative glucose concentrations, it also may have resulted in a greater frequency of hypoglycemia. Identification of hypoglycemic symptoms is especially challenging in an unconscious patient, and the prognosis of hypoglycemia remains unclear.

Drs. Rius and Mauricio noted a difference in some patient characteristics between the 2 study groups at baseline (for example, aspirin use), which may be a reasonable explanation for the increased incidence of strokes and deaths in the intensive treatment group. The small number of events makes it difficult to draw firm conclusions about stroke and death despite the fact that these reached statistical significance. The issue in interpreting the data, we believe, is not whether the distribution of events is too extreme to have occurred by chance alone, but rather whether such few events should drive clinical policy. We clearly think this would be misguided until more trials or a much larger trial become available.

Potential Financial Conflicts of Interest: None disclosed.