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Volume 6, Number 3, 2004

Mary Ann Liebert, Inc.

Experience with the Continuous Glucose Monitoring

System in a Medical Intensive Care Unit




Strict glycemic control improves clinical outcomes in critically ill patients. However, practi-
cal tools for frequent monitoring of blood glucose (BG) levels in the intensive care unit (ICU)
are limited. The Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed,
Northridge, CA) is currently approved for detecting glycemic excursions in outpatients with
diabetes mellitus. The use of this device has never been carefully examined in the inpatient
setting. This preliminary study was designed to investigate the accuracy of the CGMS in crit-
ically ill patients admitted to a medical ICU (MICU). Subjects at risk for hyperglycemia were
recruited from among all patients admitted to our MICU. CGMS sensors were implanted for
up to 72 h. Study subjects wore between one and five consecutive sensors. Four or more stan-
dard capillary BG readings were recorded per 24 h. All paired metersensor (M-S) readings
were used both for CGMS calibration and for data analysis. Twenty-two MICU patients wore
41 CGMS sensors, yielding 546 M-S BG pairs. Overall, the Pearson correlation coefficient (r)
was 0.88, with a mean M-S difference of 3.3 6 26.7 mg/dL (0.6 6 17.4%) and a mean absolute
M-S difference of 19.7 6 18.3 mg/dL (12.8 6 11.9%). Clarke Error Grid analysis categorized
98.7% of the M-S pairs within clinically acceptable zones A and B. The CGMS is promis-
ing for potential use in critically ill patients. If validated in larger studies, the device could
serve as a useful research tool for investigating the role of hyperglycemia (and strict glyce-
mic control) in ICU patients. If further developed as a real-time glucose sensor, CGMS tech-
nology could ultimately prove clinically useful in the ICU, by decreasing nursing workload
and/or by providing alarm signals for impending glycemic excursions.

BACKGROUND infusion protocol (IIP) to maintain strict nor-

moglycemia (80110 mg/dL) reduced mortal-

M ETICULOUS CONTROL of blood glucose (BG)

concentrations reduces morbidity and
mortality in critically ill patients. In Leuven,
ity in a surgical intensive care unit (ICU) by
42%.1 In this landmark study, strict BG control
also lowered the incidence of bloodstream in-
Belgium, the use of an intravenous (IV) insulin fections, acute renal failure, anemia requiring

Sections of 1 Endocrinology, 2Pulmonary & Critical Care, and 3Cardiovascular Medicine, Department of Internal
Medicine; 4 Department of Nursing; and 5General Clinical Research Center, Yale New Haven Hospital, Yale Univer-
sity School of Medicine, New Haven, Connecticut.
The data presented in this paper were presented (in preliminary form) as a poster at the 63rd Scientific Sessions of
the American Diabetes Association, held in New Orleans, Louisiana, in June 2003.


blood transfusions, and the need for prolonged day. CGMS readings must be calibrated at least
ventilatory support. Strict glycemic control ap- four times daily against standard capillary BG
pears to have clinical benefits in other intensive measurements, which are used to retrospec-
care settings as well. Following myocardial tively calibrate the sensor readings at the time
infarction, for example, the use of an IV in- of data analysis. This FDA-approved approach
sulinglucose infusion (followed by an outpa- uses modified linear regression to determine
tient multidose subcutaneous insulin regimen) and correct for several calibration factors. In
improved long-term prognosis in patients with outpatients with diabetes, the CGMS provides
diabetes mellitus (DM).2,3 In patients having reasonable correlation with circulating BG lev-
open heart surgery, the use of a perioperative els (see below). Implanted sensor sites gener-
IIP reduced the incidence of deep sternal ally maintain their reliability for up to 72 h.810
wound infections in patients with diabetes to Despite extensive studies in outpatients with
that of the population without diabetes.4,5 DM, use of the CGMS has never been carefully
Based on these and other clinical studies, examined in the inpatient setting. Theoreti-
there are growing efforts worldwide to better cally, disruptive clinical issues such as subcu-
understand the role of hyperglycemia in the taneous edema, hypotension, and the use of va-
ICU, and to improve glycemic control in criti- sopressor therapy could impact upon the
cally ill patients. Unfortunately, there are many accuracy and reliability of the device.
practical barriers to achieving these goals. First, In the ICU setting, a reliable, accurate contin-
strict BG control requires extensive nursing ef- uous glucose monitor would provide a valuable
forts, including frequent bedside glucose mon- research tool for studying the impact of BG lev-
itoring and the implementation of complex els on critically ill patients. Additionally, if the
IIPs. Second, the preferred method of glucose CGMS could be further developed as a real-
testing is a matter of debate; the use of stan- time glucose monitor, it could ease nursing
dard capillary glucose monitoring (finger- workload in the ICU by greatly reducing the
sticks) may be inaccurate in hypotensive pa- number of manual BG tests required to main-
tients,6 while frequent sampling of arterial or tain strict BG control. The development of an
venous blood may lead to excess phlebotomy. alarm system to detect impending glycemic
Finally, a prevalent fear of hypoglycemia excursions would also be very useful clinically.
among hospital staff serves as a potent barrier This preliminary study was performed to in-
to the widespread implementation of strict IIPs. vestigate the efficacy and safety of the CGMS
At the present time, there are no validated in critically ill patients admitted to a medical
mechanisms for continuously monitoring BG ICU (MICU).
levels in hospitalized patients. As a result, there
exist no alarms that could alert the nursing staff
to impending hypo- or hyperglycemia in ICU
The Continuous Glucose Monitoring System
Clinical setting
(CGMS, Medtronic MiniMed, Northridge, CA)
is currently approved by the U.S. Food and This study took place in the 14-bed MICU of
Drug Administration (FDA) as a retrospec- the Yale New Haven Hospital, a 944-bed ter-
tive Holter-style glucose monitor.7 In clinical tiary care referral center located in New Haven,
practice, it is used primarily for guiding insulin CT. Nearly 40% of the Yale MICU patients are
dose adjustments in outpatients with diabetes. admitted for primary respiratory disease.
The CGMS uses a glucose oxidase-based plat- Other common diagnoses (together accounting
inum electrode to measure an electrical current for another one-third of admissions) include
that relates to interstitial fluid glucose concen- gastrointestinal hemorrhage, sepsis/hypoten-
tration. This current is transmitted to a pager- sion, acute renal failure, hyperglycemic crises,
sized monitor, which analyzes incoming data and primary cardiovascular events. In the
every 10 s and stores a smoothed, filtered glu- MICU, the patient-to-nurse ratio is either 1:1 or
cose average every 5 min, i.e., 288 readings per 2:1. The annual in-MICU mortality rate is 14%.

Subject recruitment tered 6090 min after sensor insertion. For all
study subjects, MICU nurses obtained a mini-
Subjects for this study were recruited from
mum of four fingersticks every 24 h; all mea-
among all patients admitted to the MICU. Pa-
sured capillary BG values were entered into the
tients expected to stay for ,24 h, e.g., admit-
CGMS system.
ted for observation following a procedure,
Persistent sensor malfunction was defined
were excluded from enrollment, as were
by the appearance of an error message on the
boarder patients, e.g., overflow postopera-
CGMS that could not be remedied within 1 h.
tive patients, not primarily cared for by the
In all cases, such malfunction occurred because
MICU physician staff. Patients were selected
of an unacceptably low sensor current, sug-
for participation based on the presence of hy-
gesting loss of proper contact between the elec-
perglycemia (BG $ 200 mg/dL), a clinical his-
trode and the interstitial fluid.
tory of DM, or the use of one or more clinical
interventions known to be associated with hy-
Data analysis
perglycemia in the MICU: corticosteroids, va-
sopressors, and/or enteral/parenteral nutri- Following data acquisition, CGMS devices
tion.11 were downloaded using the MiniMed Com-
Station. Sensor BG values were calculated us-
Data collection methods ing proprietary software (MiniMed Graphs
Version 1.7 and MiniMed Solutions Version
Our study protocol was approved by the
3.0). Concurrent glucose meter and sensor BG
Yale University School of Medicine Human In-
values were compared by calculating both the
vestigation Committee. Informed consent was
mean difference (MD 5 meter BG 2 sensor
obtained from all study subjects and/or their
BG) and mean absolute difference (MAD 5
families. All data were collected prospectively,
uMDu) between BG values, expressed both in
from the active hospital chart and MICU nurs-
mg/dL and as a percentage. A Pearson corre-
ing records. Admission clinical variables in-
lation coefficient (r) was calculated for the en-
cluded age, sex, race, height, weight, history of
tire set of metersensor (M-S) pairs. Finally,
DM, and an Acute Physiology And Chronic
paired M-S values were plotted on a Clarke Er-
Health Evaluation II (APACHE II) score.12
ror Grid,13 which has been accepted by the FDA
APACHE II provides a validated severity of ill-
as a valid supplement to the review of contin-
ness score based on 12 readily accessible clini-
uous glucose measurements. 14 Except where
cal and laboratory parameters (heart rate,
noted, all clinical data are expressed as mean 6
hematocrit, etc.). Reasons for ICU admission
standard deviation (SD), or as a percentage.
and the use of relevant clinical interventions
(nutrition therapy, corticosteroids, vasopres-
sors) were also collected. All study subjects
were followed until discharge from the MICU. RESULTS
Capillary (fingerstick) BG levels were mea-
sured using a standard hospital glucose meter Twenty-four patients and/or their families
(Surestep Flexx, Lifescan, Johnson & Johnson, were approached for study enrollment. Two of
Milpitas, CA). All glucose meters were cali- the 24 declined study participation. Baseline
brated on a daily basis. CGMS sensors were in- characteristics and relevant clinical interven-
serted using the Sen-Serter device (Medtronic tions for the 22 enrolled study subjects are
MiniMed). Sensors were placed in the lateral shown in Table 1. Thirteen (59%) patients had
abdomen, or in the upper, outer portion of the known DM; five of these 13 were insulin-de-
buttocks. Transparent tape was then used to se- pendent. The median BG level upon ICU ad-
cure the sensors to the skin. MICU nurses mission was 175 mg/dL (interquartile range,
and/or one of the investigators inspected the 134279 mg/dL).
site at least twice daily for signs of local irrita- In total, 41 CGMS sensors were worn (one to
tion, infection, or bleeding. To allow time for five sensors per patient), yielding 546 paired
calibration, the first recorded BG value was en- M-S values for analysis. These M-S BG pairs are

TABLE 1. BASELINE CHARACTERISTICS AND of absolute BG levels on measured M-S differ-

Notably, our study did not test the accuracy
IIP patients of the CGMS during hypoglycemic conditions.
Characteristic (n 5 22) Of the 546 M-S pairs obtained, only four had
Age (years) 61 6 15
BG levels ,60 mg/dL using either method of
Male (%) 50% BG measurement. In three of these four in-
Race (%) stances, the CGMS value was lower than the
Caucasian 55% corresponding meter BG level. In one case, a
African American 36%
Hispanic 5% meter BG level of 40 mg/dL was assigned a
Other 5% value of 89 mg/dL by the CGMS.
Body mass index (kg/m2) 28.8 6 11.0 In this study, the presence of DM did not sig-
APACHE II score 20.0 6 6.80
Primary diagnosis (%) nificantly affect the accuracy of the CGMS. The
Respiratory failure 50% MD% for M-S pairs from patients with diabetes
Hyperglycemic crisis 18% was 0.5 6 19.1% (vs. 0.8 6 15.2% for patients
Sepsis/hypotension 14%
Primary cardiovascular events 9%
without diabetes, P 5 0.86), while the MAD%
Other 9% was 13.6 6 13.5% (vs. 11.8 6 9.5%, P 5 0.07).
Clinical interventions (%) The use of vasopressors also did not affect sen-
Corticosteroid therapy 59% sor accuracy. The MD% for M-S pairs from pa-
Vasopressor therapy 32%
Enteral nutrition 68% tients on vasopressor therapy was 0.0 6 16.9%
Parenteral nutrition 9% (vs. 1.1 6 17.9% for patients not on vasopres-
sors, P 5 0.47), while the MAD% was 11.8 6
All data are expressed as mean 6 SD, or as a percent-
age. 12.0% (vs. 13.5 6 11.7%, P 5 0.10). Because we
enrolled only 22 subjects, this study lacked the
power to assess the impact of individual clini-
cal diagnoses on CGMS performance.
plotted in Figure 1. For all 546 pairs, the MD Results of the Clarke Error Grid analysis are
was 3.3 6 26.7 mg/dL (0.6 6 17.4%), and the shown in Figure 3. Of the 546 M-S pairs, 78.4%
MAD was 19.7 6 18.3 mg/dL (12.8 6 11.9%). fell within Zone A, indicating agreement
The overall r was 0.88. Overall, 63.4% of M-S within 20% (or agreement on hypoglycemia),
pairs fell within 20 mg/dL of one another, 20.3% fell within Zone B, indicating a M-S dif-
while 87.8% fell within 40 mg/dL. Aside from ference of more than 20% that would not likely
cases of persistent sensor malfunction prior to result in treatment error, and only 1.3% fell
72 h (seven of the 41 sensors), only 16 of 562 within Zones CE, indicating that these pairs
(2.9%) meter values were not assigned a paired would likely have lead to a treatment error. In
sensor reading. In all of these cases, a tem- summary, then, 98.7% of the 546 M-S pairs
porarily low sensor current was responsible for were judged as clinically acceptable using
the lack of data. Clarke Error Grid criteria.
To determine the effects of absolute BG lev- There were no serious adverse events re-
els on M-S differences, we separately analyzed ported during use of the CGMS. In two patients
the M-S pairs by absolute BG value. For this (both receiving anticoagulant), mild bleeding
analysis, shown in Table 2, mean M-S BG occurred during sensor insertion. In one sub-
levels were employed in order to minimize ject, the bleeding stopped quickly with gentle
measurement bias. As expected, MAD rose pressure. In the second, an alternate sensor site
slowly as absolute BG levels increased, from was needed to achieve timely hemostasis. In-
15.4 mg/dL when BG was ,100 mg/dL to 28.7 terestingly, these two events did not appear to
when BG was $ 250 mg/dL. However, MAD% affect subsequent CGMS measurements. Other
decreased with higher absolute BG levels, from than the single sensor insertion described
20.0% when BG was ,100 mg/dL to 9.8% when above, no CGMS sensors had to be removed
BG was $ 250 mg/dL. A BlandAltman plot,15 because of local pain, irritation, or bleeding,
shown in Figure 2, visually displays the impact and there were no infectious complications.

FIG. 1. Scatter plot of the 546 M-S BG pairs. BG values from the CCGMS are shown on the y-axis. BG values from
the referent glucose meter are shown on the x-axis.

Seven of the 41 sensors (17%) exhibited per- sensors failed prior to 72 h; as a result, this
sistent sensor malfunction prior to 72 h. In one subject accounted for nearly one-half of
one subject (a thin 83-year-old man with dia- our studys persistent sensor malfunctions.
betes admitted for an exacerbation of chronic Following detailed review of this subjects
obstructive pulmonary disease, who re- CGMS data, it was clear that his sensor cur-
mained normotensive throughout his ex- rents were continuously low during all three
tended ICU stay), three of three implanted of his sensor placements.


Mean BG (mg/dL) MD MAD

Mean M-S BG value
(mg/dL) Number of M-S pairs Meter Sensor mg/dL % mg/dL %

,100 43 82.3 82.4 20.1 23.4 15.4 20.0

100149 219 127.5 122.7 24.8 22.1 17.3 13.5
150199 185 173.3 171.4 1.9 20.2 19.7 11.3
200249 66 221.8 216.1 5.7 1.4 25.7 11.4
$250 33 295.6 294.8 0.8 20.9 28.7 9.8

To minimize measurement bias, mean M-S BG values (shown in the leftmost column) were used to categorize the
BG data. Note that while MADs (in mg/dL) climbed with rising BG levels, MADs by percent became smaller at higher
BG concentrations.

FIG. 2. BlandAltman plot15 for the 546 M-S pairs. Mean M-S BG levels are shown on the x-axis. The y-axis displays
M-S BG differences.

DISCUSSION AND CONCLUSIONS betes. 810 In an early company-sponsored

study,8 62 subjects with diabetes utilized the
This preliminary study was performed to in- CGMS for up to 3 weeks, yielding over 300,000
vestigate the accuracy of the CGMS in critically individual sensor readings and more than 9,000
ill patients admitted to an MICU. The accuracy paired M-S values. Daily correlation coeffi-
and reliability of the CGMS have been previ- cients showed decent trend agreement, with a
ously demonstrated in outpatients with dia- median daily r 5 0.92. Overall, sensor readings

FIG. 3. Scatter plot of the 562 M-S BG pairs using Clarke Error Grid analysis (see text for explanation). BG values
from the CGMS are shown on the y-axis, while BG values from the referent glucose meter are shown on the x-axis.
Percentages of M-S pairs falling within each zone of the Clarke Error Grid are shown. Using this method, 98.7% of
M-S pairs were clinically acceptable, falling within Zone A or B.

were 5.4 6 44.2 mg/dL below standard meter with diabetes,2022 it should be noted that le-
readings, with a MD% of 20.3% 6 32.4%. A gitimate concerns have been raised about
follow-up study of 135 patients yielded similar the reproducibility of BG measurements ob-
results, with r 5 0.91, MAD% 5 18.0 6 19.8%, tained from CGMS monitoring.23 In addi-
and a Clarke Error Grid analysis showing tion, the accuracy of the CGMS is unavoid-
96.2% of M-S pairs within clinically acceptable ably affected by the accuracy of the referent
zones A and B.9 A larger postmarketing study glucose measurement. In hypotensive pa-
in 238 patients reported a similar r (0.91) and a tients, for example, capillary (fingerstick)
MAD% of 12.6%; in this study, age, race, and BG determinations may underestimate cir-
the type/duration of DM were found to have culating BG levels.6 Despite this finding, fin-
no impact upon the accuracy of the device.10 gersticks remain the standard method for
Importantly, CGMS measurements appear to BG measurement in many ICUs. During our
be reliable under conditions of hypo- and hy- study, we elected to use standard capillary
perglycemia, 16,17 and seem unaffected by am- readings as the BG referent, primarily to best
bient insulin concentrations. 18 The accuracy of allow comparisons with previously pub-
the CGMS may improve slightly when calibra- lished outpatient studies. However, future
tions are performed by an experienced nurse.19 studies comparing CGMS readings to arter-
To date, however, this technology has not been ial (or venous) blood will be required before
validated in the inpatient setting. use of the CGMS can be validated in the ICU
In our study, the accuracy of the CGMS in setting.
the MICU compared favorably with its accu- 2. Hypoglycemia detection. Though prior studies
racy in outpatients with DM. In 22 MICU pa- suggest unaltered CGMS accuracy during
tients, we found an MD of 3.3 6 26.7 mg/dL hypoglycemia,15,16 small BG differences can
(0.6 6 17.4%), a MAD of 19.7 6 18.3 mg/dL have significant clinical relevance when the
(12.8 6 11.9%), and an overall r of 0.88. As ex- levels fall into the hypoglycemic range. This
pected, MAD rose slightly during hyper- point has important implications for the po-
glycemia. However, MAD% fell as BG levels tential clinical use of the CGMS as a real-
climbed. In other words, when analyzed by per- time glucose monitor. In our study, limited
cent difference, the accuracy of the CGMS im- subject numbers prohibited a meaningful
proved at higher BG levels. Finally, using exploration of the CGMS accuracy during
Clarke Error Grid analysis, 98.7% of the CGMS hypoglycemia. A larger, prospective study
readings in our study were deemed clinically performed in patients on intensive IIPs will
acceptable; this compares favorably with the be required to validate use of the CGMS un-
96.2% rate published in outpatient studies.9 der hypoglycemic conditions.
Though our study subject numbers were too 3. Retrospective data. An important limitation of
small for detailed statistical analyses, poten- the current CGMS is its function as a ret-
tially disruptive clinical issues such as edema, rospective glucose monitor. At the present
hypotension, and vasopressor therapy (all of time, data from the monitor can be accessed
which were present in some of our patients) only after the completion of a 72-h data col-
did not appear to affect the accuracy of the lection period. Before the CGMS can be re-
CGMS. We hypothesize that both the sedentary lied upon clinically, extensive inpatient
nature and the supervised environment of studies using real-time CGMS technology
MICU patients contributed significantly to the will be required. In addition, for optimal
devices accuracy in this setting. clinical application, the creation and valida-
The results of this preliminary study should tion of an ICU-specific error grid (designed
be interpreted with the following important to test how the CGMS guides an IV insulin
caveats: infusion) will likely be required.

1. Accuracy of the CGMS. Though several pub- In conclusion, this preliminary study sug-
lished studies have demonstrated clinical gests that the CGMS is promising for potential
benefit employing the CGMS in outpatients use in ICU patients. The device appears to pro-

vide similar accuracy in critically ill MICU pa- wound infection in diabetics after open heart opera-
tients as compared with outpatients with DM. tions. Ann Thor Surg 1997;63:356361.
5. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A: Con-
We believe that the CGMS could serve as a use-
tinuous intravenous insulin infusion reduces the in-
ful research tool for investigating the role of hy- cidence of deep sternal wound infection in diabetic
perglycemia (and strict glycemic control) in crit- patients after cardiac surgical procedures. Ann Thor
ically ill patients. If further developed as a Surg 1999;67:352362.
real-time glucose sensor, CGMS technology 6. Atkin SH, Dasmahapatra A, Jaker M, Chorost MI,
Reddy S: Fingerstick glucose determination in shock.
may also prove clinically useful in the ICU, by
Ann Intern Med 1991;114:10201024.
decreasing nursing workload and/or by pro- 7. Mastrototaro JJ: The MiniMed continuous glucose
viding alarm signals for impending glycemic ex- monitoring system. Diabetes Technol Ther 2000;2
cursions. Such technology would address the (Suppl 1):S13S18.
most important barriers to the successful imple- 8. Gross TM, Mastrototaro JJ: Efficacy and reliability of
mentation of intensive insulin infusions, and the continuous glucose monitoring system. Diabetes
Technol Ther 2000;2(Suppl 1):S19S26.
would likely facilitate the use of such protocols
9. Gross TM, Bode BW, Einhorn D, Kayne DM, Reed JH,
in critically ill patients. In turn, improved glyce- White NH, Mastrototaro JJ: Performance evaluation
mic control in the ICU could lead to reduced of the MiniMed coninuous glucose monitoring sys-
morbidity and mortality in critically ill patients. tem during patient home use. Diabetes Technol Ther
10. Gross TM, Ter Veer A: Continuous glucose monitor-
ACKNOWLEDGMENTS ing in previously unstudied population subgroups.
Diabetes Technol Ther 2000;2(Suppl 1):S27S34.
CGMS monitors, sensors, software, and an- 11. Inzucchi S, Goldberg P, Dziura J, Siegel M, Lee M,
Halickman J, Sherwin R: Risk factors for poor glyce-
cillary equipment for this study were provided
mic control in a medical intensive care unit (MICU)
by Medtronic MiniMed Corp., Northridge, CA. [abstract]. Diabetes 2003;52(Suppl 1):A96.
Additional unrestricted study funds were pro- 12. Knaus WA, Draper EA, Wagner DP, Zimmerman JE:
vided by Eli Lilly and Co., Indianapolis, IN. Dr. APACHE II: a severity of disease classification sys-
Goldberg was supported by Juvenile Diabetes tem. Crit Care Med 1985;13:818829.
Research Foundation fellowship grant JDRF-3- 13. Clarke WL, Cox D, Gonder-Frederick LA, Carter W,
Pils SL: Evaluating clinical efficacy of systems for self-
2003-95. Study support was also derived from
monitoring of blood glucose. Diabetes Care 1987;10:
Yales General Clincial Research Center, Na- 622628.
tional Institutes of Health center grant MO1 14. Food and Drug Administration: Review Criteria As-
RR-00125. sessment of Portable Glucose Monitoring In Vitro Di-
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