Clinical impact of sample interference on intensive insulin therapy in severely burned patients: a pilot study

Abstract

Severely burned patients benefit from intensive insulin therapy (IIT) for tight glycemic control (TGC). The authors evaluated the clinical impact of automatic correction of hematocrit and ascorbic acid interference for bedside glucose monitoring performance in critically ill burn patients. The performance of two point-of-care glucose monitoring systems (GMSs): 1) GMS1, an autocorrecting device, and 2) GMS2, a noncorrecting device were compared. Sixty remnant arterial blood samples were collected in a prospective observational study to evaluate hematocrit and ascorbic acid effects on GMS1 vs GMS2 accuracy paired against a plasma glucose reference. Next, we enrolled 12 patients in a pilot randomized controlled trial. Patients were randomized 1:1 to receive IIT targeting a TGC interval of 111 to 151 mg/dl and guided by either GMS1 or GMS2. GMS bias, mean insulin rate, and glycemic variability were calculated. In the prospective study, GMS1 results were similar to plasma glucose results (mean bias, -0.75 [4.0] mg/dl; n = 60; P = .214). GMS2 results significantly differed from paired plasma glucose results (mean bias, -5.66 [18.7] mg/dl; n = 60; P = .048). Ascorbic acid therapy elicited significant GMS2 performance bias (29.2 [27.2]; P < .001). Randomized controlled trial results reported lower mean bias (P < .001), glycemic variability (P < .05), mean insulin rate (P < .001), and frequency of hypoglycemia (P < .001) in the GMS1 group than in the GMS2 group. Anemia and high-dose ascorbic acid therapy negatively impact GMS accuracy and TGC in burn patients. Automatic correction of confounding factors improves glycemic control. Further studies are warranted to determine outcomes associated with accurate glucose monitoring during IIT.

Figure 1. Electrochemical Glucose Biosensor Layout

The figure illustrates a typical glucose oxidase-based electrochemical glucose biosensor. Biosensor components are identified on the right. Examples of confounding factors and the effect on each biosensor component are shown on the left.

Figure 2. Hematocrit Effects on GMS1 and GMS2

The figure shows data from the prospective observational study comparing GMS1 and GMS2 against paired plasma glucose values from the hospital laboratory. GMS bias for anemic, normocythemic, and polycythemic samples are identified. Bias is defined as the GMS minus the plasma glucose value.

Figure 3. High Dose Ascorbic Acid Therapy Interference Case Examples

The figure shows two case examples of high dose ascorbic acid therapy interference on GMS1 vs. GMS2 when compared to paired hospital plasma glucose results. Panel A is a case involving a 21 year old woman with poly-trauma including 90% TBSA burns. Panel B is a case involving a 29 year old man with 90% TBSA burns. Arrows indicate the start and stop times for the high dose ascorbic acid therapy. Ascorbic acid dosing was 500 mg/kg in 1L of Lactated Ringers solution infused over a 24 hour period.

Figure 3. High Dose Ascorbic Acid Therapy Interference Case Examples

The figure shows two case examples of high dose ascorbic acid therapy interference on GMS1 vs. GMS2 when compared to paired hospital plasma glucose results. Panel A is a case involving a 21 year old woman with poly-trauma including 90% TBSA burns. Panel B is a case involving a 29 year old man with 90% TBSA burns. Arrows indicate the start and stop times for the high dose ascorbic acid therapy. Ascorbic acid dosing was 500 mg/kg in 1L of Lactated Ringers solution infused over a 24 hour period.

Figure 4. Hematocrit Correction During Intensive Insulin Therapy

Two case examples illustrating hematocrit effects on GMS1 vs. GMS2 when compared to paired hospital plasma glucose measurements. Paired hematocrit measurements are also reported. All measurements were made every 12 hours. Panel A is a case involving a 37 year old man with 37% TBSA burns assigned to the GMS1 group. Panel B is a case involving a 38 year old woman with 45.5% TBSA burns assigned to the GMS2 group. GMS2 measurements exhibited significant bias. GMS2 bias was mitigated by applying the correction factor derived from the prospective observational study and representative of the patient’s mean hematocrit (−9.6 mg/dL for anemic samples).

Figure 4. Hematocrit Correction During Intensive Insulin Therapy

Two case examples illustrating hematocrit effects on GMS1 vs. GMS2 when compared to paired hospital plasma glucose measurements. Paired hematocrit measurements are also reported. All measurements were made every 12 hours. Panel A is a case involving a 37 year old man with 37% TBSA burns assigned to the GMS1 group. Panel B is a case involving a 38 year old woman with 45.5% TBSA burns assigned to the GMS2 group. GMS2 measurements exhibited significant bias. GMS2 bias was mitigated by applying the correction factor derived from the prospective observational study and representative of the patient’s mean hematocrit (−9.6 mg/dL for anemic samples).