key: cord-0324614-516cah42
authors: Boeder, S.; Kobayashi, E.; Ramesh, G.; Serences, B.; Kulasa, K.; Majithia, A. R.
title: Accuracy and Glycemic Efficacy of Continuous Glucose Monitors in Critically Ill COVID-19 Patients: a Retrospective Study
date: 2022-05-09
journal: nan
DOI: 10.1101/2022.05.06.22274685
sha: 8d2c0c8f929af540c1701a55d45f10bb8ae0134c
doc_id: 324614
cord_uid: 516cah42

Background: Continuous Glucose Monitoring (CGM) is approved for insulin dosing decisions in the ambulatory setting, but not currently for inpatients. CGM has the capacity to reduce patient-provider contact in inpatients with coronavirus disease 2019 (COVID-19), thus potentially reducing in hospital virus transmission. However, there are sparse data on the accuracy and efficacy of CGM to titrate insulin doses in inpatients. Methods: Under an emergency use protocol, CGM (Dexcom G6) was used alongside standard point-of-care (POC) glucose measurements in patients critically ill from complications of COVID-19 requiring intravenous (IV) insulin. Glycemic control during IV insulin therapy was retrospectively assessed comparing periods with and without adjunctive CGM use. Accuracy metrics were computed and Clarke Error Grid analysis performed comparing CGM glucose values with POC measurements. Results: 24 critically ill patients who met criteria for emergency use of CGM resulted in 47333 CGM and 5677 POC glucose values. During IV insulin therapy, individuals' glycemic control improved when CGM was used (mean difference -30.2 mg/dL). Among 2194 matched CGM:POC glucose pairs a high degree of concordance was observed with a MARD of 14.8% and 99.5% of CGM:POC pairs falling in Zones A and B of the Clarke Error Grid. Conclusions: CGM use in critically ill COVID-19 patients improved glycemic control during IV insulin therapy. CGM glucose data were highly concordant with POC glucose during IV insulin therapy in critically ill patients suggesting that CGM could substitute for POC measurements in inpatients thus reducing patient-provider contact and mitigating infection transmission.

Conclusions: CGM use in critically ill COVID-19 patients improved glycemic control during IV insulin therapy. CGM glucose data were highly concordant with POC glucose during IV insulin therapy in critically ill patients suggesting that CGM could substitute for POC measurements in inpatients thus reducing patient-provider contact and mitigating infection transmission.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 9, 2022 Uncontrolled hyperglycemia is associated with increased length of hospital stay and mortality. [1] Accurate blood glucose measurements are essential for safe and effective titration of insulin particularly in critically ill patients on IV insulin to achieve optimal blood glucose targets. [2] The current standard of care for measuring inpatient blood glucose for insulin dosing decision is to use point-of-care (POC) glucose meter devices which require hospital staff to manually sample patients at frequencies ranging from once every 4-6 hours for those receiving subcutaneous insulin injections, to once every 0.5 to 2 hours for those on intravenous insulin. [2] While POC is the standard of care, clinically significant glycemic events can be missed between POC tests even at the highest sampling frequency of 0.5 hours. Simply increasing the frequency of POC testing would increase burden on the hospital staff who carry out the tests and increase their exposure to COVID-19 and other transmissible infections.

Continuous glucose monitoring (CGM), which requires one sensor insertion every 10-14 days and can sample interstitial glucose every 5 minutes, has the potential to address the shortcomings of POC testing. [3] While non-adjunctive CGM has been approved by the U.S. Food and Drug Administration (FDA) for use in the ambulatory setting since 2016, [4, 5] their use in hospitals has not been approved and remains experimental despite mounting evidence that CGM improves glycemic control in inpatients. [6] [7] [8] [9] [10] The COVID-19 pandemic accelerated the adoption of CGM technology within hospitals, [11, 12] reflecting the need to reduce healthcare provider exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) while improving glycemic control in patients with diabetes who are much more likely to be hospitalized after COVID-19 infection than their counterparts without diabetes. [13, 14] In April of 2020 the FDA announced its permission for expanded utilization of remote monitoring . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 9, 2022. ; https://doi.org/10.1101/2022.05.06.22274685 doi: medRxiv preprint Page 4 of 14 devices, including the use of CGM in hospitals. [15] More recently, the FDA provided the Dexcom G6 with a breakthrough device designation.

Following the original FDA announcement, our institution developed an emergency protocol for the use of CGM in the ICU to assist with glycemic control in patients with COVID-19 related critical illness requiring intravenous insulin. Here, we report on data collected from 24 individuals relating glycemic outcomes and CGM accuracy to POC measurements. Retrospective analysis of data obtained from the Emergency Protocol was approved by the UC San Diego Institutional Review Board. Data were collected from 23 patients who wore CGM in the hospital between July 2020 and February 2021 and met the following criteria: 1) age ≥18 years, 2) admitted with confirmed COVID-19 infection to an intensive care unit at either UC San Diego Medical Center in Hillcrest or UC San Diego Jacobs Medical Center, and 3) required continuous intravenous insulin infusion therapy. One additional patient did not receive insulin infusion (IV insulin was planned but never implemented) but met all other inclusion criteria. The . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 9, 2022. ; https://doi.org/10.1101/2022.05.06.22274685 doi: medRxiv preprint Page 5 of 14 comparison of glycemic control during insulin infusion achieved with and without CGM excluded data from this patient, but the analysis of CGM accuracy included this patient. CGM data were downloaded using Dexcom CLARITY software. POC glucose data and patient information, including demographics and medical history, were extracted from the electronic health record (EHR) system. Non-numeric glucose value entries were filtered and POC data points with glucose values of less than 20mg/dL were removed as they were considered artifacts.

Data analysis and plotting were implemented in Python 3.9.7 using the standard library, Glycemic control during periods 'on' and 'off' CGM was assessed by comparing POC glucose values during periods of IV insulin infusion with or without CGM use. A Kolmogorov-Smirnov (KS) test and a two-sided student t-test were used to determine statistical significance. CGM and POC pairs were matched based on timepoints, where each POC datapoint was matched with a CGM datapoint within 5 minutes. Clarke Error Grid analysis was computed using a publicly available Python script (https://github.com/suetAndTie/ClarkeErrorGrid) modified to allow for shading zones in different colors. Mean absolute relative difference (MARD) was calculated as previously described. [16] Results:

Characteristics of the patients included in the study (n=24) are shown in Table 1 .

Participants were predominantly male (75%) with poorly controlled diabetes (mean A1c 9.8%) and diagnosed with COVID-19 pneumonia/ respiratory failure. Almost all participants required ventilatory (n=23) and hemodynamic (n=22) support with an eventual mortality rate of 54%. For each participant, periods of IV insulin therapy were extracted from the EHR and intersected with . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 9, 2022. A major strength of our study includes enrollment of participants with COVID-19 related critical illness. Almost all participants required ventilatory support and over half required hemodynamic support with vasopressors -conditions that could theoretically impact interstitial glucose levels and decrease the concordance between CGM and blood glucose. These factors suggest that the observed concordance of CGM and POC glucose meter values (99.5% Clarke Error Grid zones A and B) is likely a conservative estimate and in the general, non-critically ill inpatient population clinical concordance is likely to be even higher. Furthermore, the improved glycemic control observed during CGM-on versus CGM-off times during intravenous insulin was observed in almost all individual participants (21/23). Taken together, these findings support the use of CGM in critically ill COVID-19 patients in place of POC glucose meters, a timely . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 9, 2022. ; https://doi.org/10.1101/2022.05.06.22274685 doi: medRxiv preprint Page 8 of 14 finding given the trend towards increased infectiousness of newly arising SARS-COV2 variants. [17, 18] Our study has several limitations including a retrospective study design, a relatively small sample size, and lack of a CGM only group. Since patients were not prospectively enrolled, a cryptic bias in the individuals enrolled under the emergency use protocol could confound our findings. Despite a relatively small number of individuals enrolled (n=24), our study is among the largest testing CGM use in critically ill patients to date [7, 11, [19] [20] [21] [22] [23] and the amount of analyzable CGM and POC glucose data obtained (n=47333 CGM values, n=5677 POC values) drives statistically robust inferences. The lack of a CGM only group prevents us from being able to formally test non-adjunctive CGM based insulin titration, but our study evidentiates the safety and potential efficacy of a CGM based insulin titration that needs prospective validation.

Continuous glucose monitors have not been widely studied in the ICU and have not been approved for inpatient use. In our study of critically ill COVID-19 positive patients on IV insulin, we observe improved glycemic control with adjunctive CGM use compared to standard point of care testing alone. This finding was driven by a reduction in hyperglycemia, which translated to an improvement in average blood glucose during CGM use in 91% of participants.

Additionally, CGM demonstrated high concordance with POC, suggesting that it can substitute for POC glucose measurements during IV insulin titration. CGM use would reduce patient provider contact, thereby reducing in hospital transmission of infectious illness such as SARS-Cov2.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 9, 2022. 

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Blue lines indicate an increase in average blood glucose when off CGM. Red lines denote a decrease in average blood glucose when off CGM.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Two data points fell outside the range of this graph (POC glucose above 400mg/dL) but would have fallen in the A or B zones.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 9, 2022. ; https://doi.org/10.1101/2022.05.06.22274685 doi: medRxiv preprint

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