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American Journal of Critical Care. 2008;17: 150-156
Copyright © 2008 by the American Association of Critical-Care Nurses.
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Improvement of Glucose Control in the Intensive Care Unit: An Interdisciplinary Collaboration Study

By Ulrike Holzinger, MD, Monika Feldbacher, RN, Adelbert Bachlechner, RN, Reinhard Kitzberger, MD, Valentin Fuhrmann, MD and Christian Madl, MD. All authors work in the intensive care unit of the Division of Gastroenterology and Hepatology in the Department of Internal Medicine III at the Medical University of Vienna, Vienna, Austria.

Corresponding author: Ulrike Holzinger, MD, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, ICU, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria (e-mail: ulrike.holzinger{at}meduniwien.ac.at).


   Abstract
Top
 Abstract
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Background Strict glycemic control in critically ill patients is challenging for both physicians and nurses.

Objectives To determine the effect of focused education of intensive care staff followed by implementation of a glucose control protocol.

Methods A prospective observational study in a medical intensive care unit in a university hospital. After intensive education of nurses and physicians, a glucose control protocol with a nurse-managed insulin therapy algorithm was developed and implemented. Every measured blood glucose value and insulin dose per hour and per day were documented in 36 patients before and 44 patients after implementation of the protocol.

Results Median blood glucose levels decreased after implementation of the protocol (133 vs 110 mg/dL; P < .001). The amounts of time when patients’ blood glucose levels were less than 110 mg/dL and less than 150 mg/dL increased after implementation of the protocol (8% vs 44%; 75% vs 96%; P<.001). The median use of insulin increased after implementation of the protocol (28 vs 35 IU/day; P=.002). Diabetic patients had higher median blood glucose levels than did nondiabetic patients both before (138 vs 131 mg/dL) and after (115 vs 108 mg/dL; P<.001) implementation, although median insulin use also increased (before implementation, 33 vs 26 IU/day; P=.04; after implementation, 46 vs 30 IU/day; P < .001).

Conclusions Use of a collaboratively developed glucose control protocol led to decreased median blood glucose levels and to longer periods of normoglycemia. Despite increased insulin use, glucose control was worse in diabetic patients.

The metabolic response to stress, characterized by enhanced gluconeogenesis and peripheral insulin resistance, frequently leads to hyperglycemia in critically ill patients.1–4 Hyperglycemia is associated with a higher mortality and morbidity in critically ill surgical and medical patients.5,6 Moreover, hyperglycemia promotes complications such as critical illness polyneuropathy, bacteremia, and acute renal failure.5

In one study,5 introducing intensive insulin therapy guided by an algorithm with a target blood glucose level between 80 and 110 mg/dL (to convert to millimoles per liter, multiply by 0.055) led to a 42% relative reduction in mortality in the intensive care unit (ICU). In medical patients who stayed more than 3 days in the ICU, mortality and morbidity could also be significantly reduced by intensive insulin therapy.6 In a study7 with a historical control group, researchers were able to show a survival benefit that resulted from introducing an intensive glucose management protocol intended to keep blood glucose levels less than 140 mg/dL in a heterogeneous population of critically ill patients. Consequently, the Surviving Sepsis Campaign recommends that blood glucose levels be kept at less than 150 mg/dL for all ICU patients.8

However, strict glycemic control in critically ill patients poses a challenge for both physicians and nurses in the ICU. Although many ICUs intend to use strict glycemic control, physicians and nurses may not understand the importance of maintaining glycemic control in critically ill patients.9 For example, in a multicenter study,9 only 79.8% of the physicians and 58.4% of the nurses in an ICU considered avoidance of hyperglycemia important in patients with myocardial infarction. Exchange of information and cooperation between physicians and nurses in the ICU are essential for successful implementation of intensive insulin therapy.10 Kanji et al10 found that having a nurse-managed algorithm for intensive insulin therapy was more effective (patients reached the target blood glucose values faster and stayed within the target range longer) than having the insulin therapy administered at a physician’s discretion.

We hypothesized that intensive education of physicians and nurses in the ICU followed by the establishment of a glucose control protocol (developed by the entire ICU staff) that included a nurse-managed insulin therapy algorithm would lead to decreased median blood glucose levels and to longer periods of normoglycemia in critically ill patients.


   Materials and Methods
Top
 Abstract
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Setting
The medical ICU at the General Hospital Vienna, a university hospital with 2000 beds, has 8 beds and a staff of 6 intensivists and 30 nurses. In 2004, staff in the ICU treated 351 patients for a total of 2839 patient-days. On 57% of these days, patients received mechanical ventilation. Mean length of stay was 8.1 days per patient. Mean age was 59 years; 60% of the patients were male, 40% were female. Mean score on the Acute Physiology and Chronic Health Evaluation III at admission was 69. Overall ICU mortality was 21% and hospital mortality was 32%. A total of 89% of all patients had at least 24 hours of continuous intravenous insulin therapy during their ICU stay.


Patients reach blood glucose targets faster and stay within targets longer with nurse-managed insulin therapy than they do with therapy at the physician’s discretion.

 

Nutritional support in our ICU is standardized according to a protocol. Energy requirements for ICU patients are calculated as 25 kcal per kilogram body weight per day. Patients are prescribed 50% of calculated energy requirements on day 1, 75% on day 2, and 100% from day 3 on. If no contraindications exist, patients receive enteral nutrition via a gastric feeding tube. The nutritional protocol was not changed throughout the whole study.

Interventions
During a 3-month observational baseline period (January to April 2004), 36 consecutively admitted critically ill medical patients who stayed in the ICU longer than 48 hours and who received continuous intravenous insulin for more than 24 hours were included in the study. During this 3-month period, every measured blood glucose concentration and the daily insulin requirements were documented. Insulin therapy during this period was at the physician’s discretion. Since the Leuven study5 in 2001, doctors have pursued tighter glucose control; however, the target range has not been uniform. Moreover, no algorithm was used.


The number of hypoglycemic events was similar before and after implementation of the protocol.

 

Thereafter, all 6 physicians and 30 nurses working in the medical ICU attended 5 different mandatory educational sessions that conveyed the importance of strict glycemic control. In the first 3 sessions, background data and evidence-based findings were presented and discussed among the ICU staff. In the fourth session, target levels for blood glucose were defined, and difficulties or challenges of the intensive insulin therapy were identified. Moreover, suggestions for measures supporting glucose control were collected, and, finally, the glucose control protocol was developed by both the nurses and the physicians. The final version of the protocol was presented in the fifth session. Collaboration of physicians and nurses guaranteed that the protocol met not only the medical requirements but also was practical enough to be applied clinically. All 5 sessions were cochaired by the director and the head nurse of the medical ICU.

Information about the importance of glucose control in the ICU and detailed information about the glucose control protocol were distributed via e-mail to all ICU staff (both nurses and physicians).

The protocol contained the following measures:


Figure 1
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  		Figure Algorithm for intensive insulin therapy in a medical intensive care unit.

 
After implementation of the protocol, during a 3-month interventional period (September to December 2004), 44 patients who stayed in the ICU longer than 48 hours and who received continuous intravenous insulin for more than 24 hours were included in the study.

Instruments/Measures
Nurses in the ICU used an ABL 700 blood gas analyzer (Radiometer, Copenhagen, Denmark) to measure glucose levels in arterial blood during both periods.

The interventional protocol complied with the Declaration of Helsinki. Because the implementation of the glucose control protocol was exclusively aimed at physicians and nurses, the local review committee waived the requirement for getting consent from patients.

Statistical Analysis
Data are expressed as median (interquartile range). Area under the curve was calculated to measure the lengths of time that patients’ blood glucose levels were less than 110 mg/dL and less than 150 mg/dL. The Mann-Whitney U test was used to compare differences between numeric parameters when appropriate. Statistical analysis was done with the GraphPad Prism 4.00 software program (GraphPad Software, Inc, San Diego, California). A P of .05 or less was considered significant.


   Results
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 Abstract
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
The reasons for ICU admission of all patients are given in Table 1Go. Age, weight, height, score on the Acute Physiology and Chronic Health Evaluation III, and length of stay did not differ between the 2 periods (Table 2Go). Blood glucose values and insulin use for all patients are given in Table 2Go. Insulin use increased significantly after the glucose control protocol was implemented, and median blood glucose levels decreased significantly. The rate of hypoglycemic events remained unchanged after the protocol was implemented. The length of time that patients’ blood glucose levels were less than 110 mg/dL and less than 150 mg/dL increased significantly after the glucose control protocol was implemented.


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  		Table 1 Reasons for admission to the intensive care unita

 

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  		Table 2 Characteristics of patientsa

 
Of the 36 patients observed before the protocol was implemented, 14 (39%) were diabetic and 2 of the 14 had type 1 diabetes (insulin dependent). Of the 44 patients observed after implementation of the protocol, 16 (36%) were diabetic and 4 of the 16 had type 1 diabetes. Subgroup analyses of diabetic and nondiabetic patients are given in Table 3Go. Insulin use and median blood glucose levels were significantly greater in the subgroup with diabetes in both periods. The length of time that patients’ blood glucose levels were less than 110 mg/dL did not differ between the 2 subgroups before the protocol was implemented. After the protocol was implemented, the length of time that patients’ blood glucose levels were less than 110 mg/dL was significantly shorter in the diabetic patients than in the nondiabetic patients. The length of time that patients’ blood glucose levels were less than 150 mg/dL was significantly greater in the non-diabetic patients than in the diabetic patients in both periods.


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  		Table 3 Subgroup analysis of diabetic and nondiabetic patientsa

 

Insulin use and median blood glucose levels were higher in the diabetic subgroup.

 

In both subgroups, insulin use increased significantly and median blood glucose levels decreased significantly after implementation of the glucose control protocol. The lengths of time that patients’ blood glucose levels were less than 110 mg/dL and were less than 150 mg/dL increased significantly after implementation of the protocol in both subgroups.


Blood glucose levels were lower in patients receiving continuous versus bolus corticosteroid therapy.

 

The percentage of patients receiving corticosteroid therapy did not differ before and after implementation of the protocol (before, n=19, 53%; after, n=19, 43%; P=.39). Subgroup analysis of patients receiving corticosteroid therapy revealed that blood glucose levels of patients receiving continuous corticosteroid therapy were significantly lower than levels in patients receiving bolus corticosteroid therapy: before, 131 (110–155) mg/dL; after, 110 (94–131) mg/dL; P <.01.


Nurse-physician collaboration in the insulin protocol development met medical as well as practical drug administration requirements.

 


   Discussion
Top
 Abstract
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
Numerous studies have shown the adverse effects of hyperglycemia in different diseases.13–18 The Leuven studies5,6 have shown the benefit of normoglycemia with respect to morbidity and mortality in critically ill patients. However, achieving normoglycemia in critically ill patients in daily clinical practice has been a greater challenge than expected. A lack of information about the importance of normoglycemia in critically ill patients is widespread in ICUs.9 Cooperation between nurses and physicians leads to improved glucose control and a higher success rate at achieving normoglycemia.10 However, other factors also may influence glucose control in critically ill patients.

In our study, implementation of a glucose control protocol that included a nurse-managed insulin therapy algorithm and several other supporting measures improved glucose control in a medical ICU and led to normoglycemia a high percentage of the time.

As Kanji et al10 have shown, information about the importance of strict glycemic control is essential. Moreover, intensive insulin therapy given according to an algorithm and managed by nurses leads to better results than does insulin therapy administered at physicians’ discretion.10 Therefore, we arranged 5 mandatory educational sessions for nurses and physicians working in our 8-bed ICU. We assumed that ensuring that nurses and physicians had the same information would improve cooperation between them. This high level of knowledge in nurses and physicians facilitated collaborative development and then implementation of the glucose control protocol and may in part have been responsible for the observed improvement in the glucose control.

In the Leuven studies,5,6 normoglycemia in critically ill patients was achieved by the introduction of an insulin therapy algorithm. One of the measures of our glucose control protocol was the introduction of a similar insulin algorithm. The percentages of diabetic patients in our study (38% before and 36% after implementation of the glucose control protocol) was greater than those in the Leuven studies (13% and 15.2%–17.8% diabetic patients).5,6 Therefore, our initial insulin rates were greater than those in the Leuven algorithm. To facilitate the nurse-managed insulin therapy, we posted printouts of our algorithm at every patient’s bedside. This fact and the remodeling of the patient documenting system should make the use of intensive insulin therapy at the bedside more practicable.

A major concern with implementation of intensive insulin therapy is the fear that the rate of hypoglycemia may increase and have adverse effects. In our study of patients in a medical ICU, the rate of hypoglycemia was 16%. This rate is obviously higher than that in patients in the surgical ICU in the Leuven study.5 However, the second Leuven study6 on medical patients yielded even higher hypoglycemia rates (between 18.7% and 25.1% in the intensive insulin therapy group) than those in our study. Despite the administration of a significantly higher amount of insulin after the introduction of the glucose control protocol, the rate of hypoglycemia did not increase in our patients. We observed no adverse effects of hypoglycemia.

Another measure of our glucose control protocol was the change to exclusively intravenous continuous administration of insulin, a practice that facilitates control of insulin effect.

Our results indicate that achieving normoglycemia in known diabetic patients is even more difficult than in nondiabetic patients. Before the protocol was implemented, diabetic patients received a mean of 26% more insulin than did nondiabetic patients. Despite a further increase in insulin administration (mean, 53%) in diabetic patients after the protocol was implemented, glucose control was still worse in diabetic patients than in nondiabetic patients. An underlying diabetes likely leads to an additional insulin resistance that must be considered when intensive insulin therapy is used in these patients, and a possible fear of high insulin doses therefore must be overcome. We assume that an adapted algorithm for diabetic patients with higher insulin doses could solve this problem. Because of the small number of patients with type 1 diabetes, differences in glucose control between patients with type 1 and type 2 diabetes could not be analyzed.

Corticosteroid therapy elevates blood glucose levels. However, corticosteroid therapy in critically ill patients is used in many diseases.19–21 To avoid blood glucose peaks, we started to administer corticosteroid therapy exclusively continuously, as was done in the Leuven studies. From our data, it is not clear whether continuous corticosteroid therapy can markedly improve glucose control in critically ill patients by itself. In our study, lower blood glucose levels cannot be attributed solely to the continuous corticosteroid therapy because of the concomitant implementation of the whole glucose control protocol with its multiple measures.

Each of the factors just outlined has an influence on glucose control in critically ill patients. In our study, we showed, for the first time, that consideration of all these factors leads to normoglycemia in critically ill medical patients a high percentage of the time.

This study is limited by the small number of patients included. Nevertheless, most of our results, except mortality, differed significantly before and after implementation of the glucose control protocol.


   Conclusion
Top
 Abstract
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
Our study shows the feasibility of establishing a glucose control protocol in a medical ICU. Collaboration of physicians and nurses guaranteed that the protocol not only met the medical requirements but also was practical. The collaboratively developed glucose control protocol was based on intensive education of both nurses and physicians and led to decreased median blood glucose levels and to longer periods of normoglycemia in critically ill patients. As long as no technical devices that can facilitate intensive insulin therapy are available, close collaboration between physicians and nurses in combination with a glucose control protocol seems to be the only way to accomplish intensive insulin therapy in the ICU.


Nurse-managed insulin therapy using an algorithm led to better glucose control than did insulin therapy at the physician’s discretion.

 


   ACKNOWLEDGMENTS
 
We thank all the ICU staff for participating in the educational sessions, development of the glucose control protocol, and implementation of the protocol in daily clinical practice.

To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints{at}aacn.org.

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FINANCIAL DISCLOSURES
None reported.


   REFERENCES
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 Abstract
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

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