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Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Amy
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Jarry
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Hypoglycemia in ICU

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Delay in blood glucose monitoring during an insulin infusion protocol is associated with increased risk of hypoglycemia in intensive care units

Since publication of the first randomized controlled trial of insulin infusion therapy in surgical intensive care unit (ICU) patients,1 most institutions have implemented insulin infusion protocols (IIP) for tight glycemic control in their ICUs.29 The major problem with tight glycemic control is the risk of hypoglycemia. In the randomized controlled trial involving medical ICU patients, 18.7% patients experienced at least 1 episode of blood glucose (BG) <40 mg/dL.10 Recently, a major insulin infusion trial involving patients with severe sepsis was stopped due to unacceptably high risk of hypoglycemia.11 Potential benefits of BG control may be offset by potential risks of hypoglycemia. While there can be multiple factors that could contribute to the risk of hypoglycemia, suboptimal protocol implementation is relatively amenable to correction.

Most IIPs are nurse driven. Nurses monitor BG levels every 30 to 60 minutes and make adjustments in insulin infusion rates. Each point of care testing and insulin dose adjustment takes about 5 minutes of nursing time.12 Given the numerous other nursing responsibilities for monitoring and documentation in very sick patients, nurses may not always be able check BGs at the recommended times. We investigated whether a delay in BG monitoring during insulin infusion therapy is associated with higher risk of hypoglycemia.

Methods

Data were collected for 50 consecutive patients treated with Brigham and Women's Hospital's insulin infusion protocol (BHIP) between September 27, 2006 and October 13, 2006. The investigation was part of the hospital's ongoing diabetes quality improvement program. Partners‐Health Human Research Committee approved the study. Patient demographics, history of diabetes mellitus, and glycosylated hemoglobin (A1C) were obtained from paper and electronic medical records. Point‐of‐care BG values were obtained from the bedside paper flow sheets. The exact times of individual BG measurements were ascertained from Point of Care Precision Web (QCM3.0; Abbott, Inc.).

Target BG range with BHIP is 80 to 110 mg/dL. BHIP requires BG testing every 60 minutes unless a BG value of <60 mg/dL is obtained; in which case, testing is required every 30 minutes. A time violation was assumed to have occurred if the BG was measured >70 minutes after a previous value of 60 mg/dL or >40 minutes after a previous BG value of <60 mg/dL (ie, >10 minutes after the recommended time for measurement). Although the choice of 10 minutes was arbitrary, we think it is a reasonable and practical time frame for getting a BG measurement. If a measurement was obtained earlier than the recommended time, it was not considered a time violation. However, measurements obtained within 30 minutes of a previous BG value (overwhelmingly drawn for confirmation of a previous BG value) were excluded from analysis.

BG values were divided into 2 categories: values following time violation and values following no time violation. The numbers of values in different BG ranges (<80, 80110, >110 mg/dL) were compared in the 2 categories using a chi square test. Data are presented as mean standard deviation (SD), median and numbers with percentage. Statistical significance was set at P < 0.05.

Results

Mean age of the 50 patients treated with BHIP was 64.0 13.6 years. There were 27 men and 23 women. Eighteen patients had preexisting diabetes (1 had type 1 and 17 had type 2 diabetes, mean A1C 7.1 1.7%) and 32 patients had no previous history of diabetes (mean A1C 5.9 0.9%). Mean serum creatinine was 1.34 1.0 mg/dL. Mean BG at the start of BHIP was 173 69.6 mg/dL; median 167.5 mg/dL. Mean BG during insulin infusion was 117.3 43.1 mg/dL; median 107 mg/dL. Mean BG during insulin infusion was higher in diabetic patients compared to nondiabetic patients (125.2 57.8 versus 113.4 38.8 mg/dL; P < 0.01). Monitoring for BGs was done with similar frequency in all patients. Overall, 40.2% of the total 2,605 BG values were in a range of 80 to 110 mg/dL. A total of 1.5% of values were below 60 mg/dL; only 4 values were <40 mg/dL.

A total of 2,309 values could be studied for time violations. The remaining 296 values were either obtained within 30 minutes of the previous test or the exact time of measurement could not be ascertained. A total of 1,474 (63.9%) measurements had been obtained at the recommended time or earlier than the recommended time; 835 (36.1%) measurements had been obtained >10 minutes after the recommended time for measurement (time violation). The proportion of BG values below the target (<80 mg/dL) was significantly higher following the time violation as compared to no time violation (Table 1). On the other hand, values >110 mg/dL were not more common following a time violation, compared to instances when no time violation occurred.

Time Violations and Blood Glucose Values during BHIP
Time Violation [n = 835 (100%)] No Time Violation [n = 1,474 (100%)] P Value
  • Abbreviation: NS, statistically nonsignificant.

BG values <80 mg/dL 149 (17.8) 171 (11.6) <0.001
BG values 80110 mg/dL 316 (37.8) 596 (40.4) NS
BG values >110 mg/dL 370 (44.3) 708 (47.8) NS

Frequency of time violation was similar in subgroups of patients divided according to gender, presence of diabetes and the type of ICU (Table 2). Comparison among subgroups of admission diagnoses was not possible due to the small number of patients. Overall, the proportion of low BG values was lower in diabetic patients compared to nondiabetic patients (11.9% versus 15.0%, P = 0.03). An increased rate of hypoglycemia following time violations was present in all subgroups except for the diabetic subgroup (Table 3).

Patient Characteristics and Frequency of Time Violation
Characteristic Number of Patients % of BG Values Associated with Time Violations P Value
  • Abbreviation: NS, statistically nonsignificant.

Gender NS
Male 27 36
Female 23 36
Diabetes status NS
Known diabetes 18 37
No known diabetes 32 35
Type of ICU NS
Medical 20 38
Surgical 30 35
Admission diagnosis
Cardiovascular disease 7 35
Gastrointestinal disease 4 43
Malignant disorder 8 32
Neurological disease 7 36
Orthopedic problem 2 51
Respiratory disease 13 33
Renal failure 3 46
Sepsis 6 36
Patient Characteristic and Relation of Time Violation to Hypoglycemia
% BG Values <80
Characteristic Time Violation No Time Violation P Value
  • Abbreviation: NS, statistically nonsignificant.

Male 19.1 11.9 <0.001
Female 16.1 11.2 0.03
Known diabetes 13.3 11.1 NS
No diabetes 20 11.9 <0.001
Medical ICU 19.2 11.9 0.002
Surgical ICU 16.8 11.3 0.004
Cardiovascular diseases 21.1 14.1
Gastrointestinal diseases 22.1 14.8
Malignant disorders 22.0 11.7
Neurological diseases 7.5 5.0
Orthopedic problems 6.2 6.6
Respiratory diseases 11.9 10.4
Renal failure 35.7 15.6
Sepsis 19.7 13.5

Discussion

Our study shows that a delay in BG testing during BHIP is associated with higher chances of a low BG value. This effect was consistent in multiple subgroups. However, the effect was nonsignificant in diabetic patients, probably due to higher mean BG levels and less frequent low BG values. Over one‐third of all BG measurements were obtained after a time violation. Protocol violations in our study are no different from those reported by others.7, 13, 14 Our patient characteristics of severe hypoglycemic episodes and the overall BG control achieved with BHIP were also similar to those reported by others with similar protocols.5, 7, 1517 While the results of this study may still be specific to BHIP, we think they are applicable to other similar protocols.

Because a delay in testing by itself is unlikely to cause hypoglycemia, a more likely explanation for these results is that hypoglycemia occurred when insulin infusion adjustments were not made in a timely fashion due to prolonged BG monitoring intervals. Insulin infusions are the preferred treatment in rapidly changing clinical settings because changes in insulin doses can be made frequently. Most IIPs are designed with the assumption that insulin dose adjustments will be made regularly and frequently, based on BG measurements. Although there is no gold standard for the optimal BG test frequency, in most protocols BG testing is performed every hour in order to ensure safety as well as efficacy. Our results are consistent with the intuitive assumption that a timely measurement of the BG is important for successful implementation of an IIP.

It was somewhat surprising that high BG values were not more frequent following a time violation. We can only speculate as to the reason for this. It is possible that critically ill patients are near maximally insulin resistant and, once an effective insulin infusion rate is achieved, further increases are not as frequently required. On the other hand, insulin requirements may decrease rapidly as contributors to insulin resistance resolve. Another possibility is that there may be a limit to hepatic glucose production during acute illness making patients more prone to hypoglycemia. It is also possible that the nurses tend to test more promptly when the BG levels are running high. Thus, the insulin doses may be increased at proper times until BG levels are in the target range. However, when BG levels are in the target range, nurses may become less vigilant, leading to a delay in testing. As a result a decrease in insulin dose, when required, does not happen as promptly as an increase in dose.

In our study the absolute risk of hypoglycemia associated with time violation was 6%. Avoiding this hypoglycemia may have an impact on glycemic control in the ICU and may change clinical outcomes. Moreover, this is 1 of the few factors that are potentially amenable to correction. Therefore, measures to improve adherence to protocols, eg, prompts for BG testing and better nurse training regarding importance of timely testing, may reduce the risk of hypoglycemia.

References
  1. van den Berghe G,Wouters P,Weekers F, et al.Intensive insulin therapy in the surgical intensive care unit.N Engl J Med.2001;345(19):13591367.
  2. Krinsley JS.Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.Mayo Clin Proc.2004;79(8):9921000.
  3. Laver S,Preston S,Turner D,McKinstry C,Padkin A.Implementing intensive insulin therapy: development and audit of the Bath insulin protocol.Anaesth Intensive Care.2004;32(3):311316.
  4. Lien LF,Spratt SE,Woods Z,Osborne KK,Feinglos MN.Optimizing hospital use of intravenous insulin therapy: improved management of hyperglycemia and error reduction with a new nomogram.Endocr Pract.2005;11(4):240253.
  5. Taylor BE,Schallom ME,Sona CS, et al.Efficacy and safety of an insulin infusion protocol in a surgical ICU.J Am Coll Surg.2006;202(1):19.
  6. Goldberg PA,Siegel MD,Sherwin RS, et al.Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27(2):461467.
  7. DeSantis AJ,Schmeltz LR,Schmidt K, et al.Inpatient management of hyperglycemia: the Northwestern experience.Endocr Pract.2006;12(5):491505.
  8. Rea RS,Donihi AC,Bobeck M, et al.Implementing an intravenous insulin infusion protocol in the intensive care unit.Am J Health Syst Pharm.2007;64(4):385395.
  9. Quinn JA,Snyder SL,Berghoff JL,Colombo CS,Jacobi J.A practical approach to hyperglycemia management in the intensive care unit: evaluation of an intensive insulin infusion protocol.Pharmacotherapy.2006;26(10):14101420.
  10. Van den Berghe G,Wilmer A,Hermans G, et al.Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354(5):449461.
  11. Brunkhorst FM,Engel C,Bloos F, et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med.2008;358(2):125139.
  12. Aragon D.Evaluation of nursing work effort and perceptions about blood glucose testing in tight glycemic control.Am J Crit Care.2006;15(4):370377.
  13. Oeyen SG,Hoste EA,Roosens CD,Decruyenaere JM,Blot SI.Adherence to and efficacy and safety of an insulin protocol in the critically ill: a prospective observational study.Am J Crit Care.2007;16(6):599608.
  14. Clayton SB,Mazur JE,Condren S,Hermayer KL,Strange C.Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit.Crit Care Med.2006;34(12):29742978.
  15. Collier B,Diaz J,Forbes R, et al.The impact of a normoglycemic management protocol on clinical outcomes in the trauma intensive care unit.JPEN J Parenter Enteral Nutr.2005;29(5):353358.
  16. Kanji S,Singh A,Tierney M,Meggison H,McIntyre L,Hebert PC.Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults.Intensive Care Med.2004;30(5):804810.
  17. Bland DK,Fankhanel Y,Langford E, et al.Intensive versus modified conventional control of blood glucose level in medical intensive care patients: a pilot study.Am J Crit Care.2005;14(5):370376.
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Journal of Hospital Medicine - 4(6)
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E5-E7
Legacy Keywords
hypoglycemia, ICU, insulin infusion
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Article PDF

Since publication of the first randomized controlled trial of insulin infusion therapy in surgical intensive care unit (ICU) patients,1 most institutions have implemented insulin infusion protocols (IIP) for tight glycemic control in their ICUs.29 The major problem with tight glycemic control is the risk of hypoglycemia. In the randomized controlled trial involving medical ICU patients, 18.7% patients experienced at least 1 episode of blood glucose (BG) <40 mg/dL.10 Recently, a major insulin infusion trial involving patients with severe sepsis was stopped due to unacceptably high risk of hypoglycemia.11 Potential benefits of BG control may be offset by potential risks of hypoglycemia. While there can be multiple factors that could contribute to the risk of hypoglycemia, suboptimal protocol implementation is relatively amenable to correction.

Most IIPs are nurse driven. Nurses monitor BG levels every 30 to 60 minutes and make adjustments in insulin infusion rates. Each point of care testing and insulin dose adjustment takes about 5 minutes of nursing time.12 Given the numerous other nursing responsibilities for monitoring and documentation in very sick patients, nurses may not always be able check BGs at the recommended times. We investigated whether a delay in BG monitoring during insulin infusion therapy is associated with higher risk of hypoglycemia.

Methods

Data were collected for 50 consecutive patients treated with Brigham and Women's Hospital's insulin infusion protocol (BHIP) between September 27, 2006 and October 13, 2006. The investigation was part of the hospital's ongoing diabetes quality improvement program. Partners‐Health Human Research Committee approved the study. Patient demographics, history of diabetes mellitus, and glycosylated hemoglobin (A1C) were obtained from paper and electronic medical records. Point‐of‐care BG values were obtained from the bedside paper flow sheets. The exact times of individual BG measurements were ascertained from Point of Care Precision Web (QCM3.0; Abbott, Inc.).

Target BG range with BHIP is 80 to 110 mg/dL. BHIP requires BG testing every 60 minutes unless a BG value of <60 mg/dL is obtained; in which case, testing is required every 30 minutes. A time violation was assumed to have occurred if the BG was measured >70 minutes after a previous value of 60 mg/dL or >40 minutes after a previous BG value of <60 mg/dL (ie, >10 minutes after the recommended time for measurement). Although the choice of 10 minutes was arbitrary, we think it is a reasonable and practical time frame for getting a BG measurement. If a measurement was obtained earlier than the recommended time, it was not considered a time violation. However, measurements obtained within 30 minutes of a previous BG value (overwhelmingly drawn for confirmation of a previous BG value) were excluded from analysis.

BG values were divided into 2 categories: values following time violation and values following no time violation. The numbers of values in different BG ranges (<80, 80110, >110 mg/dL) were compared in the 2 categories using a chi square test. Data are presented as mean standard deviation (SD), median and numbers with percentage. Statistical significance was set at P < 0.05.

Results

Mean age of the 50 patients treated with BHIP was 64.0 13.6 years. There were 27 men and 23 women. Eighteen patients had preexisting diabetes (1 had type 1 and 17 had type 2 diabetes, mean A1C 7.1 1.7%) and 32 patients had no previous history of diabetes (mean A1C 5.9 0.9%). Mean serum creatinine was 1.34 1.0 mg/dL. Mean BG at the start of BHIP was 173 69.6 mg/dL; median 167.5 mg/dL. Mean BG during insulin infusion was 117.3 43.1 mg/dL; median 107 mg/dL. Mean BG during insulin infusion was higher in diabetic patients compared to nondiabetic patients (125.2 57.8 versus 113.4 38.8 mg/dL; P < 0.01). Monitoring for BGs was done with similar frequency in all patients. Overall, 40.2% of the total 2,605 BG values were in a range of 80 to 110 mg/dL. A total of 1.5% of values were below 60 mg/dL; only 4 values were <40 mg/dL.

A total of 2,309 values could be studied for time violations. The remaining 296 values were either obtained within 30 minutes of the previous test or the exact time of measurement could not be ascertained. A total of 1,474 (63.9%) measurements had been obtained at the recommended time or earlier than the recommended time; 835 (36.1%) measurements had been obtained >10 minutes after the recommended time for measurement (time violation). The proportion of BG values below the target (<80 mg/dL) was significantly higher following the time violation as compared to no time violation (Table 1). On the other hand, values >110 mg/dL were not more common following a time violation, compared to instances when no time violation occurred.

Time Violations and Blood Glucose Values during BHIP
Time Violation [n = 835 (100%)] No Time Violation [n = 1,474 (100%)] P Value
  • Abbreviation: NS, statistically nonsignificant.

BG values <80 mg/dL 149 (17.8) 171 (11.6) <0.001
BG values 80110 mg/dL 316 (37.8) 596 (40.4) NS
BG values >110 mg/dL 370 (44.3) 708 (47.8) NS

Frequency of time violation was similar in subgroups of patients divided according to gender, presence of diabetes and the type of ICU (Table 2). Comparison among subgroups of admission diagnoses was not possible due to the small number of patients. Overall, the proportion of low BG values was lower in diabetic patients compared to nondiabetic patients (11.9% versus 15.0%, P = 0.03). An increased rate of hypoglycemia following time violations was present in all subgroups except for the diabetic subgroup (Table 3).

Patient Characteristics and Frequency of Time Violation
Characteristic Number of Patients % of BG Values Associated with Time Violations P Value
  • Abbreviation: NS, statistically nonsignificant.

Gender NS
Male 27 36
Female 23 36
Diabetes status NS
Known diabetes 18 37
No known diabetes 32 35
Type of ICU NS
Medical 20 38
Surgical 30 35
Admission diagnosis
Cardiovascular disease 7 35
Gastrointestinal disease 4 43
Malignant disorder 8 32
Neurological disease 7 36
Orthopedic problem 2 51
Respiratory disease 13 33
Renal failure 3 46
Sepsis 6 36
Patient Characteristic and Relation of Time Violation to Hypoglycemia
% BG Values <80
Characteristic Time Violation No Time Violation P Value
  • Abbreviation: NS, statistically nonsignificant.

Male 19.1 11.9 <0.001
Female 16.1 11.2 0.03
Known diabetes 13.3 11.1 NS
No diabetes 20 11.9 <0.001
Medical ICU 19.2 11.9 0.002
Surgical ICU 16.8 11.3 0.004
Cardiovascular diseases 21.1 14.1
Gastrointestinal diseases 22.1 14.8
Malignant disorders 22.0 11.7
Neurological diseases 7.5 5.0
Orthopedic problems 6.2 6.6
Respiratory diseases 11.9 10.4
Renal failure 35.7 15.6
Sepsis 19.7 13.5

Discussion

Our study shows that a delay in BG testing during BHIP is associated with higher chances of a low BG value. This effect was consistent in multiple subgroups. However, the effect was nonsignificant in diabetic patients, probably due to higher mean BG levels and less frequent low BG values. Over one‐third of all BG measurements were obtained after a time violation. Protocol violations in our study are no different from those reported by others.7, 13, 14 Our patient characteristics of severe hypoglycemic episodes and the overall BG control achieved with BHIP were also similar to those reported by others with similar protocols.5, 7, 1517 While the results of this study may still be specific to BHIP, we think they are applicable to other similar protocols.

Because a delay in testing by itself is unlikely to cause hypoglycemia, a more likely explanation for these results is that hypoglycemia occurred when insulin infusion adjustments were not made in a timely fashion due to prolonged BG monitoring intervals. Insulin infusions are the preferred treatment in rapidly changing clinical settings because changes in insulin doses can be made frequently. Most IIPs are designed with the assumption that insulin dose adjustments will be made regularly and frequently, based on BG measurements. Although there is no gold standard for the optimal BG test frequency, in most protocols BG testing is performed every hour in order to ensure safety as well as efficacy. Our results are consistent with the intuitive assumption that a timely measurement of the BG is important for successful implementation of an IIP.

It was somewhat surprising that high BG values were not more frequent following a time violation. We can only speculate as to the reason for this. It is possible that critically ill patients are near maximally insulin resistant and, once an effective insulin infusion rate is achieved, further increases are not as frequently required. On the other hand, insulin requirements may decrease rapidly as contributors to insulin resistance resolve. Another possibility is that there may be a limit to hepatic glucose production during acute illness making patients more prone to hypoglycemia. It is also possible that the nurses tend to test more promptly when the BG levels are running high. Thus, the insulin doses may be increased at proper times until BG levels are in the target range. However, when BG levels are in the target range, nurses may become less vigilant, leading to a delay in testing. As a result a decrease in insulin dose, when required, does not happen as promptly as an increase in dose.

In our study the absolute risk of hypoglycemia associated with time violation was 6%. Avoiding this hypoglycemia may have an impact on glycemic control in the ICU and may change clinical outcomes. Moreover, this is 1 of the few factors that are potentially amenable to correction. Therefore, measures to improve adherence to protocols, eg, prompts for BG testing and better nurse training regarding importance of timely testing, may reduce the risk of hypoglycemia.

Since publication of the first randomized controlled trial of insulin infusion therapy in surgical intensive care unit (ICU) patients,1 most institutions have implemented insulin infusion protocols (IIP) for tight glycemic control in their ICUs.29 The major problem with tight glycemic control is the risk of hypoglycemia. In the randomized controlled trial involving medical ICU patients, 18.7% patients experienced at least 1 episode of blood glucose (BG) <40 mg/dL.10 Recently, a major insulin infusion trial involving patients with severe sepsis was stopped due to unacceptably high risk of hypoglycemia.11 Potential benefits of BG control may be offset by potential risks of hypoglycemia. While there can be multiple factors that could contribute to the risk of hypoglycemia, suboptimal protocol implementation is relatively amenable to correction.

Most IIPs are nurse driven. Nurses monitor BG levels every 30 to 60 minutes and make adjustments in insulin infusion rates. Each point of care testing and insulin dose adjustment takes about 5 minutes of nursing time.12 Given the numerous other nursing responsibilities for monitoring and documentation in very sick patients, nurses may not always be able check BGs at the recommended times. We investigated whether a delay in BG monitoring during insulin infusion therapy is associated with higher risk of hypoglycemia.

Methods

Data were collected for 50 consecutive patients treated with Brigham and Women's Hospital's insulin infusion protocol (BHIP) between September 27, 2006 and October 13, 2006. The investigation was part of the hospital's ongoing diabetes quality improvement program. Partners‐Health Human Research Committee approved the study. Patient demographics, history of diabetes mellitus, and glycosylated hemoglobin (A1C) were obtained from paper and electronic medical records. Point‐of‐care BG values were obtained from the bedside paper flow sheets. The exact times of individual BG measurements were ascertained from Point of Care Precision Web (QCM3.0; Abbott, Inc.).

Target BG range with BHIP is 80 to 110 mg/dL. BHIP requires BG testing every 60 minutes unless a BG value of <60 mg/dL is obtained; in which case, testing is required every 30 minutes. A time violation was assumed to have occurred if the BG was measured >70 minutes after a previous value of 60 mg/dL or >40 minutes after a previous BG value of <60 mg/dL (ie, >10 minutes after the recommended time for measurement). Although the choice of 10 minutes was arbitrary, we think it is a reasonable and practical time frame for getting a BG measurement. If a measurement was obtained earlier than the recommended time, it was not considered a time violation. However, measurements obtained within 30 minutes of a previous BG value (overwhelmingly drawn for confirmation of a previous BG value) were excluded from analysis.

BG values were divided into 2 categories: values following time violation and values following no time violation. The numbers of values in different BG ranges (<80, 80110, >110 mg/dL) were compared in the 2 categories using a chi square test. Data are presented as mean standard deviation (SD), median and numbers with percentage. Statistical significance was set at P < 0.05.

Results

Mean age of the 50 patients treated with BHIP was 64.0 13.6 years. There were 27 men and 23 women. Eighteen patients had preexisting diabetes (1 had type 1 and 17 had type 2 diabetes, mean A1C 7.1 1.7%) and 32 patients had no previous history of diabetes (mean A1C 5.9 0.9%). Mean serum creatinine was 1.34 1.0 mg/dL. Mean BG at the start of BHIP was 173 69.6 mg/dL; median 167.5 mg/dL. Mean BG during insulin infusion was 117.3 43.1 mg/dL; median 107 mg/dL. Mean BG during insulin infusion was higher in diabetic patients compared to nondiabetic patients (125.2 57.8 versus 113.4 38.8 mg/dL; P < 0.01). Monitoring for BGs was done with similar frequency in all patients. Overall, 40.2% of the total 2,605 BG values were in a range of 80 to 110 mg/dL. A total of 1.5% of values were below 60 mg/dL; only 4 values were <40 mg/dL.

A total of 2,309 values could be studied for time violations. The remaining 296 values were either obtained within 30 minutes of the previous test or the exact time of measurement could not be ascertained. A total of 1,474 (63.9%) measurements had been obtained at the recommended time or earlier than the recommended time; 835 (36.1%) measurements had been obtained >10 minutes after the recommended time for measurement (time violation). The proportion of BG values below the target (<80 mg/dL) was significantly higher following the time violation as compared to no time violation (Table 1). On the other hand, values >110 mg/dL were not more common following a time violation, compared to instances when no time violation occurred.

Time Violations and Blood Glucose Values during BHIP
Time Violation [n = 835 (100%)] No Time Violation [n = 1,474 (100%)] P Value
  • Abbreviation: NS, statistically nonsignificant.

BG values <80 mg/dL 149 (17.8) 171 (11.6) <0.001
BG values 80110 mg/dL 316 (37.8) 596 (40.4) NS
BG values >110 mg/dL 370 (44.3) 708 (47.8) NS

Frequency of time violation was similar in subgroups of patients divided according to gender, presence of diabetes and the type of ICU (Table 2). Comparison among subgroups of admission diagnoses was not possible due to the small number of patients. Overall, the proportion of low BG values was lower in diabetic patients compared to nondiabetic patients (11.9% versus 15.0%, P = 0.03). An increased rate of hypoglycemia following time violations was present in all subgroups except for the diabetic subgroup (Table 3).

Patient Characteristics and Frequency of Time Violation
Characteristic Number of Patients % of BG Values Associated with Time Violations P Value
  • Abbreviation: NS, statistically nonsignificant.

Gender NS
Male 27 36
Female 23 36
Diabetes status NS
Known diabetes 18 37
No known diabetes 32 35
Type of ICU NS
Medical 20 38
Surgical 30 35
Admission diagnosis
Cardiovascular disease 7 35
Gastrointestinal disease 4 43
Malignant disorder 8 32
Neurological disease 7 36
Orthopedic problem 2 51
Respiratory disease 13 33
Renal failure 3 46
Sepsis 6 36
Patient Characteristic and Relation of Time Violation to Hypoglycemia
% BG Values <80
Characteristic Time Violation No Time Violation P Value
  • Abbreviation: NS, statistically nonsignificant.

Male 19.1 11.9 <0.001
Female 16.1 11.2 0.03
Known diabetes 13.3 11.1 NS
No diabetes 20 11.9 <0.001
Medical ICU 19.2 11.9 0.002
Surgical ICU 16.8 11.3 0.004
Cardiovascular diseases 21.1 14.1
Gastrointestinal diseases 22.1 14.8
Malignant disorders 22.0 11.7
Neurological diseases 7.5 5.0
Orthopedic problems 6.2 6.6
Respiratory diseases 11.9 10.4
Renal failure 35.7 15.6
Sepsis 19.7 13.5

Discussion

Our study shows that a delay in BG testing during BHIP is associated with higher chances of a low BG value. This effect was consistent in multiple subgroups. However, the effect was nonsignificant in diabetic patients, probably due to higher mean BG levels and less frequent low BG values. Over one‐third of all BG measurements were obtained after a time violation. Protocol violations in our study are no different from those reported by others.7, 13, 14 Our patient characteristics of severe hypoglycemic episodes and the overall BG control achieved with BHIP were also similar to those reported by others with similar protocols.5, 7, 1517 While the results of this study may still be specific to BHIP, we think they are applicable to other similar protocols.

Because a delay in testing by itself is unlikely to cause hypoglycemia, a more likely explanation for these results is that hypoglycemia occurred when insulin infusion adjustments were not made in a timely fashion due to prolonged BG monitoring intervals. Insulin infusions are the preferred treatment in rapidly changing clinical settings because changes in insulin doses can be made frequently. Most IIPs are designed with the assumption that insulin dose adjustments will be made regularly and frequently, based on BG measurements. Although there is no gold standard for the optimal BG test frequency, in most protocols BG testing is performed every hour in order to ensure safety as well as efficacy. Our results are consistent with the intuitive assumption that a timely measurement of the BG is important for successful implementation of an IIP.

It was somewhat surprising that high BG values were not more frequent following a time violation. We can only speculate as to the reason for this. It is possible that critically ill patients are near maximally insulin resistant and, once an effective insulin infusion rate is achieved, further increases are not as frequently required. On the other hand, insulin requirements may decrease rapidly as contributors to insulin resistance resolve. Another possibility is that there may be a limit to hepatic glucose production during acute illness making patients more prone to hypoglycemia. It is also possible that the nurses tend to test more promptly when the BG levels are running high. Thus, the insulin doses may be increased at proper times until BG levels are in the target range. However, when BG levels are in the target range, nurses may become less vigilant, leading to a delay in testing. As a result a decrease in insulin dose, when required, does not happen as promptly as an increase in dose.

In our study the absolute risk of hypoglycemia associated with time violation was 6%. Avoiding this hypoglycemia may have an impact on glycemic control in the ICU and may change clinical outcomes. Moreover, this is 1 of the few factors that are potentially amenable to correction. Therefore, measures to improve adherence to protocols, eg, prompts for BG testing and better nurse training regarding importance of timely testing, may reduce the risk of hypoglycemia.

References
  1. van den Berghe G,Wouters P,Weekers F, et al.Intensive insulin therapy in the surgical intensive care unit.N Engl J Med.2001;345(19):13591367.
  2. Krinsley JS.Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.Mayo Clin Proc.2004;79(8):9921000.
  3. Laver S,Preston S,Turner D,McKinstry C,Padkin A.Implementing intensive insulin therapy: development and audit of the Bath insulin protocol.Anaesth Intensive Care.2004;32(3):311316.
  4. Lien LF,Spratt SE,Woods Z,Osborne KK,Feinglos MN.Optimizing hospital use of intravenous insulin therapy: improved management of hyperglycemia and error reduction with a new nomogram.Endocr Pract.2005;11(4):240253.
  5. Taylor BE,Schallom ME,Sona CS, et al.Efficacy and safety of an insulin infusion protocol in a surgical ICU.J Am Coll Surg.2006;202(1):19.
  6. Goldberg PA,Siegel MD,Sherwin RS, et al.Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27(2):461467.
  7. DeSantis AJ,Schmeltz LR,Schmidt K, et al.Inpatient management of hyperglycemia: the Northwestern experience.Endocr Pract.2006;12(5):491505.
  8. Rea RS,Donihi AC,Bobeck M, et al.Implementing an intravenous insulin infusion protocol in the intensive care unit.Am J Health Syst Pharm.2007;64(4):385395.
  9. Quinn JA,Snyder SL,Berghoff JL,Colombo CS,Jacobi J.A practical approach to hyperglycemia management in the intensive care unit: evaluation of an intensive insulin infusion protocol.Pharmacotherapy.2006;26(10):14101420.
  10. Van den Berghe G,Wilmer A,Hermans G, et al.Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354(5):449461.
  11. Brunkhorst FM,Engel C,Bloos F, et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med.2008;358(2):125139.
  12. Aragon D.Evaluation of nursing work effort and perceptions about blood glucose testing in tight glycemic control.Am J Crit Care.2006;15(4):370377.
  13. Oeyen SG,Hoste EA,Roosens CD,Decruyenaere JM,Blot SI.Adherence to and efficacy and safety of an insulin protocol in the critically ill: a prospective observational study.Am J Crit Care.2007;16(6):599608.
  14. Clayton SB,Mazur JE,Condren S,Hermayer KL,Strange C.Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit.Crit Care Med.2006;34(12):29742978.
  15. Collier B,Diaz J,Forbes R, et al.The impact of a normoglycemic management protocol on clinical outcomes in the trauma intensive care unit.JPEN J Parenter Enteral Nutr.2005;29(5):353358.
  16. Kanji S,Singh A,Tierney M,Meggison H,McIntyre L,Hebert PC.Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults.Intensive Care Med.2004;30(5):804810.
  17. Bland DK,Fankhanel Y,Langford E, et al.Intensive versus modified conventional control of blood glucose level in medical intensive care patients: a pilot study.Am J Crit Care.2005;14(5):370376.
References
  1. van den Berghe G,Wouters P,Weekers F, et al.Intensive insulin therapy in the surgical intensive care unit.N Engl J Med.2001;345(19):13591367.
  2. Krinsley JS.Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.Mayo Clin Proc.2004;79(8):9921000.
  3. Laver S,Preston S,Turner D,McKinstry C,Padkin A.Implementing intensive insulin therapy: development and audit of the Bath insulin protocol.Anaesth Intensive Care.2004;32(3):311316.
  4. Lien LF,Spratt SE,Woods Z,Osborne KK,Feinglos MN.Optimizing hospital use of intravenous insulin therapy: improved management of hyperglycemia and error reduction with a new nomogram.Endocr Pract.2005;11(4):240253.
  5. Taylor BE,Schallom ME,Sona CS, et al.Efficacy and safety of an insulin infusion protocol in a surgical ICU.J Am Coll Surg.2006;202(1):19.
  6. Goldberg PA,Siegel MD,Sherwin RS, et al.Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27(2):461467.
  7. DeSantis AJ,Schmeltz LR,Schmidt K, et al.Inpatient management of hyperglycemia: the Northwestern experience.Endocr Pract.2006;12(5):491505.
  8. Rea RS,Donihi AC,Bobeck M, et al.Implementing an intravenous insulin infusion protocol in the intensive care unit.Am J Health Syst Pharm.2007;64(4):385395.
  9. Quinn JA,Snyder SL,Berghoff JL,Colombo CS,Jacobi J.A practical approach to hyperglycemia management in the intensive care unit: evaluation of an intensive insulin infusion protocol.Pharmacotherapy.2006;26(10):14101420.
  10. Van den Berghe G,Wilmer A,Hermans G, et al.Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354(5):449461.
  11. Brunkhorst FM,Engel C,Bloos F, et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med.2008;358(2):125139.
  12. Aragon D.Evaluation of nursing work effort and perceptions about blood glucose testing in tight glycemic control.Am J Crit Care.2006;15(4):370377.
  13. Oeyen SG,Hoste EA,Roosens CD,Decruyenaere JM,Blot SI.Adherence to and efficacy and safety of an insulin protocol in the critically ill: a prospective observational study.Am J Crit Care.2007;16(6):599608.
  14. Clayton SB,Mazur JE,Condren S,Hermayer KL,Strange C.Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit.Crit Care Med.2006;34(12):29742978.
  15. Collier B,Diaz J,Forbes R, et al.The impact of a normoglycemic management protocol on clinical outcomes in the trauma intensive care unit.JPEN J Parenter Enteral Nutr.2005;29(5):353358.
  16. Kanji S,Singh A,Tierney M,Meggison H,McIntyre L,Hebert PC.Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults.Intensive Care Med.2004;30(5):804810.
  17. Bland DK,Fankhanel Y,Langford E, et al.Intensive versus modified conventional control of blood glucose level in medical intensive care patients: a pilot study.Am J Crit Care.2005;14(5):370376.
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Delay in blood glucose monitoring during an insulin infusion protocol is associated with increased risk of hypoglycemia in intensive care units
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Hypoglycemia in Hospitalized Patients / Garg et al.

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Provider response to insulin‐induced hypoglycemia in hospitalized patients

Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

Demographics of Patients in the Study
Number of patients 52
Age (years) 64.8 15.8
Sex (male:female), n 29:23
Preexisting diabetes, n (%)
No diabetes 17 (33%)
Type 1 diabetes 9 (17%)
Type 2 diabetes 26 (50%)
Serum creatinine (mg/dL) 2.1 1.9
Serum creatinine 2 mg/dL, n (%) 21 (40%)
BG at time of hypoglycemia (mg/dL) 52.1 9.3
Mean BG during 24 hours before hypoglycemic episode (mg/dL) 137.5 57.0
Mean BG during 24 hours after hypoglycemic episode (mg/dL) 112 74.7
Types of Subsequent Changes in Treatment and When Diabetes Specialists Agreed
Change Number of patients receiving change Number of patients for whom diabetes specialists agreed with change, n (%)
Basal insulin decreased 6 6 (100%)
Basal insulin stopped 2 0 (0%)
IV insulin changed to scheduled SC insulin 2 1 (50%)
IV insulin to SC sliding‐scale insulin 1 0 (0%)
Change in sliding‐scale insulin dose 3 1 (33%)
Sliding‐scale insulin stopped 1 1 (100%)
IV insulin started 1 1 (100%)
Sulfonylurea stopped 1 1 (100%)
Scheduled insulin changed to sliding scale 1 0 (0%)
Insulin discontinued 3 0 (0%)
No change 31 10 (32%)

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

References
  1. American College of Endocrinology and American Diabetes Association Consensus statement on inpatient diabetes and glycemic control: a call to action.Diabetes Care.2006;29:19551962.
  2. American College of Endocrinology and American Diabetes Association consensus statement on inpatient diabetes and glycemic control.Endocr Pract.2006;12:458468.
  3. Moghissi ES KG,Abad VJ,Leija DE.Current state of inpatient diabetes burden and care, and goal of the conference.Endocr Pract.2006;12(suppl 3, sddendum):110.
  4. Bode BW,Braithwaite SS,Steed RD,Davidson PC.Intravenous insulin infusion therapy: indications, methods, and transition to subcutaneous insulin therapy.Endocr Pract.2004;10(suppl 2):7180.
  5. Clayton SB,Mazur JE,Condren S,Hermayer KL,Strange C.Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit.Crit Care Med.2006;34:29742978.
  6. Goldberg PA,Siegel MD,Sherwin RS, et al.Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27:461467.
  7. Taylor BE,Schallom ME,Sona CS, et al.Efficacy and safety of an insulin infusion protocol in a surgical ICU.J Am Coll Surg.2006;202(1):19.
  8. Queale WS,Seidler AJ,Brancati FL.Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus.Arch Intern Med.1997;157:545552.
  9. Braithwaite SS,Buie MM,Thompson CL, et al.Hospital hypoglycemia: not only treatment but also prevention.Endocr Pract.2004;10(suppl 2):8999.
  10. Van den Berghe G,Wilmer A,Hermans G, et al.Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449461.
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Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

Demographics of Patients in the Study
Number of patients 52
Age (years) 64.8 15.8
Sex (male:female), n 29:23
Preexisting diabetes, n (%)
No diabetes 17 (33%)
Type 1 diabetes 9 (17%)
Type 2 diabetes 26 (50%)
Serum creatinine (mg/dL) 2.1 1.9
Serum creatinine 2 mg/dL, n (%) 21 (40%)
BG at time of hypoglycemia (mg/dL) 52.1 9.3
Mean BG during 24 hours before hypoglycemic episode (mg/dL) 137.5 57.0
Mean BG during 24 hours after hypoglycemic episode (mg/dL) 112 74.7
Types of Subsequent Changes in Treatment and When Diabetes Specialists Agreed
Change Number of patients receiving change Number of patients for whom diabetes specialists agreed with change, n (%)
Basal insulin decreased 6 6 (100%)
Basal insulin stopped 2 0 (0%)
IV insulin changed to scheduled SC insulin 2 1 (50%)
IV insulin to SC sliding‐scale insulin 1 0 (0%)
Change in sliding‐scale insulin dose 3 1 (33%)
Sliding‐scale insulin stopped 1 1 (100%)
IV insulin started 1 1 (100%)
Sulfonylurea stopped 1 1 (100%)
Scheduled insulin changed to sliding scale 1 0 (0%)
Insulin discontinued 3 0 (0%)
No change 31 10 (32%)

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

Demographics of Patients in the Study
Number of patients 52
Age (years) 64.8 15.8
Sex (male:female), n 29:23
Preexisting diabetes, n (%)
No diabetes 17 (33%)
Type 1 diabetes 9 (17%)
Type 2 diabetes 26 (50%)
Serum creatinine (mg/dL) 2.1 1.9
Serum creatinine 2 mg/dL, n (%) 21 (40%)
BG at time of hypoglycemia (mg/dL) 52.1 9.3
Mean BG during 24 hours before hypoglycemic episode (mg/dL) 137.5 57.0
Mean BG during 24 hours after hypoglycemic episode (mg/dL) 112 74.7
Types of Subsequent Changes in Treatment and When Diabetes Specialists Agreed
Change Number of patients receiving change Number of patients for whom diabetes specialists agreed with change, n (%)
Basal insulin decreased 6 6 (100%)
Basal insulin stopped 2 0 (0%)
IV insulin changed to scheduled SC insulin 2 1 (50%)
IV insulin to SC sliding‐scale insulin 1 0 (0%)
Change in sliding‐scale insulin dose 3 1 (33%)
Sliding‐scale insulin stopped 1 1 (100%)
IV insulin started 1 1 (100%)
Sulfonylurea stopped 1 1 (100%)
Scheduled insulin changed to sliding scale 1 0 (0%)
Insulin discontinued 3 0 (0%)
No change 31 10 (32%)

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

References
  1. American College of Endocrinology and American Diabetes Association Consensus statement on inpatient diabetes and glycemic control: a call to action.Diabetes Care.2006;29:19551962.
  2. American College of Endocrinology and American Diabetes Association consensus statement on inpatient diabetes and glycemic control.Endocr Pract.2006;12:458468.
  3. Moghissi ES KG,Abad VJ,Leija DE.Current state of inpatient diabetes burden and care, and goal of the conference.Endocr Pract.2006;12(suppl 3, sddendum):110.
  4. Bode BW,Braithwaite SS,Steed RD,Davidson PC.Intravenous insulin infusion therapy: indications, methods, and transition to subcutaneous insulin therapy.Endocr Pract.2004;10(suppl 2):7180.
  5. Clayton SB,Mazur JE,Condren S,Hermayer KL,Strange C.Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit.Crit Care Med.2006;34:29742978.
  6. Goldberg PA,Siegel MD,Sherwin RS, et al.Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27:461467.
  7. Taylor BE,Schallom ME,Sona CS, et al.Efficacy and safety of an insulin infusion protocol in a surgical ICU.J Am Coll Surg.2006;202(1):19.
  8. Queale WS,Seidler AJ,Brancati FL.Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus.Arch Intern Med.1997;157:545552.
  9. Braithwaite SS,Buie MM,Thompson CL, et al.Hospital hypoglycemia: not only treatment but also prevention.Endocr Pract.2004;10(suppl 2):8999.
  10. Van den Berghe G,Wilmer A,Hermans G, et al.Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449461.
References
  1. American College of Endocrinology and American Diabetes Association Consensus statement on inpatient diabetes and glycemic control: a call to action.Diabetes Care.2006;29:19551962.
  2. American College of Endocrinology and American Diabetes Association consensus statement on inpatient diabetes and glycemic control.Endocr Pract.2006;12:458468.
  3. Moghissi ES KG,Abad VJ,Leija DE.Current state of inpatient diabetes burden and care, and goal of the conference.Endocr Pract.2006;12(suppl 3, sddendum):110.
  4. Bode BW,Braithwaite SS,Steed RD,Davidson PC.Intravenous insulin infusion therapy: indications, methods, and transition to subcutaneous insulin therapy.Endocr Pract.2004;10(suppl 2):7180.
  5. Clayton SB,Mazur JE,Condren S,Hermayer KL,Strange C.Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit.Crit Care Med.2006;34:29742978.
  6. Goldberg PA,Siegel MD,Sherwin RS, et al.Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27:461467.
  7. Taylor BE,Schallom ME,Sona CS, et al.Efficacy and safety of an insulin infusion protocol in a surgical ICU.J Am Coll Surg.2006;202(1):19.
  8. Queale WS,Seidler AJ,Brancati FL.Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus.Arch Intern Med.1997;157:545552.
  9. Braithwaite SS,Buie MM,Thompson CL, et al.Hospital hypoglycemia: not only treatment but also prevention.Endocr Pract.2004;10(suppl 2):8999.
  10. Van den Berghe G,Wilmer A,Hermans G, et al.Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449461.
Issue
Journal of Hospital Medicine - 2(4)
Issue
Journal of Hospital Medicine - 2(4)
Page Number
258-260
Page Number
258-260
Publications
Publications
Article Type
Display Headline
Provider response to insulin‐induced hypoglycemia in hospitalized patients
Display Headline
Provider response to insulin‐induced hypoglycemia in hospitalized patients
Legacy Keywords
hypoglycemia, diabetes mellitus, insulin, hospitalized patient
Legacy Keywords
hypoglycemia, diabetes mellitus, insulin, hospitalized patient
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Copyright © 2007 Society of Hospital Medicine
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Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115; Fax: (617) 277‐1568
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