Tight Glucose Control May Harm Critically Ill

Tight glucose control does not benefit critically ill patients and may even be harmful because it markedly raises the risk of hypoglycemia, according to a meta-analysis.

Given these findings, “it seems appropriate that the guidelines recommending tight glucose control in all critically ill patients should be reevaluated until the results of larger, more definitive clinical trials are available,” said Dr. Renda Soylemez Wiener of the Veterans Affairs Medical Center, White River Junction, Vt., and her associates.

In 2001, a single clinical trial showed that tight glucose control reduced in-hospital mortality by a third among critically ill surgical patients. “The results of this trial were enthusiastically received and rapidly incorporated into guidelines,” and tight glucose control is now recommended for all critically ill adults and endorsed by numerous professional societies worldwide.

However, “subsequent large randomized controlled trials of tight glucose control in medical and mixed medical-surgical ICU settings … have failed to replicate this mortality benefit,” and many have reported rates of hypoglycemia as high as 40%. “Hypoglycemia is not benign in critically ill patients; it has been linked to serious neurologic events ranging from seizures to coma,” the investigators noted.

They conducted a meta-analysis of 29 controlled trials involving 8,432 adult ICU patients with a wide range of disorders who were randomly assigned to either usual care or tight glucose control—a glucose goal of less than 150 mg/dL using an insulin infusion during part or all of the ICU stay.

In-hospital mortality was not significantly different for patients kept on tight glucose control (21.6%) than for those given usual care (23.3%). There also was no difference between the two groups in the need for dialysis, Dr. Soylemez Wiener and her associates said (JAMA 2008;300:933-44).

In subgroup analyses, tight glucose control did not benefit surgical patients vs. medical patients, nor did “very tight” glucose control prove more beneficial than “moderately tight” glucose control. Sensitivity analyses of the data based on several variables that might be clinically relevant, such as disease severity, did not alter these results.

Tight glucose control did reduce the incidence of septicemia, but only among surgical ICU patients.

“On the other hand, we found clear evidence of the main harm of tight glucose control: Hypoglycemia increased roughly fivefold regardless of the ICU setting and was more common with patients receiving very tight [rather] than moderately tight glucose control,” the researchers added.

“Our meta-analysis shows that subsequent trials have not borne out the impressive results of tight glucose control promised by the initial trial” in 2001. In fact, the subjects in that initial trial received early glucose infusions and parenteral nutrition, both of which might artificially induce hyperglycemia and both of which are atypical in clinical practice. This “may have contributed to the outlying results seen in [that] trial,” the researchers noted.

In an accompanying editorial comment, Dr. Simon Finfer and Dr. Anthony Delaney of the Royal North Shore Hospital, Sydney, said that the results of this “well-conducted” and “timely” meta-analysis “may surprise many clinicians” (JAMA 2008;300:963-5).

Not only does the meta-analysis call the benefit of tight glucose control into question, it also highlights that there is no agreed standard for glycemic control, that blood glucose levels are extremely variable during the course of an ICU stay, and that bedside measurement of blood glucose can be very inaccurate, Dr. Finfer and Dr. Delaney said.

Tight glucose control does not benefit critically ill patients and may even be harmful because it markedly raises the risk of hypoglycemia, according to a meta-analysis.

Given these findings, “it seems appropriate that the guidelines recommending tight glucose control in all critically ill patients should be reevaluated until the results of larger, more definitive clinical trials are available,” said Dr. Renda Soylemez Wiener of the Veterans Affairs Medical Center, White River Junction, Vt., and her associates.

In 2001, a single clinical trial showed that tight glucose control reduced in-hospital mortality by a third among critically ill surgical patients. “The results of this trial were enthusiastically received and rapidly incorporated into guidelines,” and tight glucose control is now recommended for all critically ill adults and endorsed by numerous professional societies worldwide.

However, “subsequent large randomized controlled trials of tight glucose control in medical and mixed medical-surgical ICU settings … have failed to replicate this mortality benefit,” and many have reported rates of hypoglycemia as high as 40%. “Hypoglycemia is not benign in critically ill patients; it has been linked to serious neurologic events ranging from seizures to coma,” the investigators noted.

They conducted a meta-analysis of 29 controlled trials involving 8,432 adult ICU patients with a wide range of disorders who were randomly assigned to either usual care or tight glucose control—a glucose goal of less than 150 mg/dL using an insulin infusion during part or all of the ICU stay.

In-hospital mortality was not significantly different for patients kept on tight glucose control (21.6%) than for those given usual care (23.3%). There also was no difference between the two groups in the need for dialysis, Dr. Soylemez Wiener and her associates said (JAMA 2008;300:933-44).

In subgroup analyses, tight glucose control did not benefit surgical patients vs. medical patients, nor did “very tight” glucose control prove more beneficial than “moderately tight” glucose control. Sensitivity analyses of the data based on several variables that might be clinically relevant, such as disease severity, did not alter these results.

Tight glucose control did reduce the incidence of septicemia, but only among surgical ICU patients.

“On the other hand, we found clear evidence of the main harm of tight glucose control: Hypoglycemia increased roughly fivefold regardless of the ICU setting and was more common with patients receiving very tight [rather] than moderately tight glucose control,” the researchers added.

“Our meta-analysis shows that subsequent trials have not borne out the impressive results of tight glucose control promised by the initial trial” in 2001. In fact, the subjects in that initial trial received early glucose infusions and parenteral nutrition, both of which might artificially induce hyperglycemia and both of which are atypical in clinical practice. This “may have contributed to the outlying results seen in [that] trial,” the researchers noted.

In an accompanying editorial comment, Dr. Simon Finfer and Dr. Anthony Delaney of the Royal North Shore Hospital, Sydney, said that the results of this “well-conducted” and “timely” meta-analysis “may surprise many clinicians” (JAMA 2008;300:963-5).

Not only does the meta-analysis call the benefit of tight glucose control into question, it also highlights that there is no agreed standard for glycemic control, that blood glucose levels are extremely variable during the course of an ICU stay, and that bedside measurement of blood glucose can be very inaccurate, Dr. Finfer and Dr. Delaney said.

Tight glucose control does not benefit critically ill patients and may even be harmful because it markedly raises the risk of hypoglycemia, according to a meta-analysis.

Given these findings, “it seems appropriate that the guidelines recommending tight glucose control in all critically ill patients should be reevaluated until the results of larger, more definitive clinical trials are available,” said Dr. Renda Soylemez Wiener of the Veterans Affairs Medical Center, White River Junction, Vt., and her associates.

In 2001, a single clinical trial showed that tight glucose control reduced in-hospital mortality by a third among critically ill surgical patients. “The results of this trial were enthusiastically received and rapidly incorporated into guidelines,” and tight glucose control is now recommended for all critically ill adults and endorsed by numerous professional societies worldwide.

However, “subsequent large randomized controlled trials of tight glucose control in medical and mixed medical-surgical ICU settings … have failed to replicate this mortality benefit,” and many have reported rates of hypoglycemia as high as 40%. “Hypoglycemia is not benign in critically ill patients; it has been linked to serious neurologic events ranging from seizures to coma,” the investigators noted.

They conducted a meta-analysis of 29 controlled trials involving 8,432 adult ICU patients with a wide range of disorders who were randomly assigned to either usual care or tight glucose control—a glucose goal of less than 150 mg/dL using an insulin infusion during part or all of the ICU stay.

In-hospital mortality was not significantly different for patients kept on tight glucose control (21.6%) than for those given usual care (23.3%). There also was no difference between the two groups in the need for dialysis, Dr. Soylemez Wiener and her associates said (JAMA 2008;300:933-44).

In subgroup analyses, tight glucose control did not benefit surgical patients vs. medical patients, nor did “very tight” glucose control prove more beneficial than “moderately tight” glucose control. Sensitivity analyses of the data based on several variables that might be clinically relevant, such as disease severity, did not alter these results.

Tight glucose control did reduce the incidence of septicemia, but only among surgical ICU patients.

“On the other hand, we found clear evidence of the main harm of tight glucose control: Hypoglycemia increased roughly fivefold regardless of the ICU setting and was more common with patients receiving very tight [rather] than moderately tight glucose control,” the researchers added.

“Our meta-analysis shows that subsequent trials have not borne out the impressive results of tight glucose control promised by the initial trial” in 2001. In fact, the subjects in that initial trial received early glucose infusions and parenteral nutrition, both of which might artificially induce hyperglycemia and both of which are atypical in clinical practice. This “may have contributed to the outlying results seen in [that] trial,” the researchers noted.

In an accompanying editorial comment, Dr. Simon Finfer and Dr. Anthony Delaney of the Royal North Shore Hospital, Sydney, said that the results of this “well-conducted” and “timely” meta-analysis “may surprise many clinicians” (JAMA 2008;300:963-5).

Not only does the meta-analysis call the benefit of tight glucose control into question, it also highlights that there is no agreed standard for glycemic control, that blood glucose levels are extremely variable during the course of an ICU stay, and that bedside measurement of blood glucose can be very inaccurate, Dr. Finfer and Dr. Delaney said.