Evaluation of Continuous Lactate Monitoring Systems within a Heparinized In Vivo Porcine Model Intravenously and Subcutaneously

Abstract

We present an animal model used to evaluate the in vivo performance of electrochemical amperometric continuous lactate sensors compared to blood gas instruments. Electrochemical lactate sensors were fabricated, placed into 5 Fr central venous catheters (CVCs), and paired with wireless potentiostat devices. Following in vivo evaluation and calibration, sensors were placed within the jugular and femoral veins of a porcine subject as a preliminary assessment of in vivo measurement accuracy. The mobile electronic circuit potentiostat devices supplied the operational voltage for the sensors, measured the resultant steady-state current, and recorded the sensor response values in internal memory storages. An in vivo time trace of implanted intravenous (IV) sensors demonstrated lactate values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. Currents measured continuously from the implanted lactate sensors over 10 h were converted into lactate concentration values through use of a two-point in vivo calibration. Study shows that intravenously implanted sensors had more accurate readings, faster peak-reaching rates, and shorter peak-detection times compared to subcutaneously placed sensors. IV implanted and subcutaneously placed sensors closer to the upper body (in this case neck) showed faster response rates and more accurate measurements compared to those implanted in the lower portion of the porcine model. This study represents an important milestone not only towards continuous lactate monitoring for early diagnosis and intervention in neonatal patients with congenital heart disease undergoing cardiopulmonary bypass surgeries, but also in the intervention of critical ill patients in the Intensive Care Units or during complex surgical procedures.

Keywords: cardiopulmonary bypass surgeries; congenital heart disease; continuous blood lactate monitoring; intravenous; lactate sensors; subcutaneous.

Figure 1

Intravenous and subcutaneous implantation of eight anti-thrombotic 5 Fr. Dual lumen central venous catheters lactate sensors in the animal study. (a) Catheter lactate sensors are placed in femoral arteries, jugular veins, and subcutaneous tissues of abdomen and neck in a porcine model. (b) An anti-thrombotic 5 Fr. Dual lumen central venous catheters lactate sensor after being carefully extracted upon excision.

Figure 2

Timeline showing in vivo experimental interventions with the start and end of lactate, glucose, and respiratory challenges, along with the blood sample collection points.

Figure 3

Continuous time trace of continuous intravenous (IV) lactate sensor measurements placed intravenously in the femoral or jugular veins are shown together with measurements using a blood gas machine (diamond markers) after lactate and glucose challenges (arrows).

Figure 4

Continuous time trace of continuous subcutaneous (SubQ) lactate sensor measurements placed subcutaneously in the neck and lower abdomen shown together with measurements using a blood gas machine (diamond markers) after lactate and glucose challenges (arrows).

Figure 5

Detailed time traces of continuous intravenous (IV) and subcutaneous (SubQ) measurements of lactate sensors after (A) the first lactate challenge and (B) the second lactate challenge. Two lactate challenges were infused at 209 min and 318 min, and discrete blood gas measurements were performed at 221 min and 330 min from arterial blood samples taken via the carotid artery access line (diamond markers).

Figure 6

(A) Response times and (B) normalized average increase rates of sensors during both lactate challenges implanted intravenously in the jugular veins (n = 4) and femoral veins (n = 2), and subcutaneously in the neck (n = 4) and in the lower abdomen (n = 4). The error bar is defined as the standard error.

Figure 7

Continuous lactate measurements of implanted sensors during the glucose challenge. Dextrose was infused at 441 min, and discrete blood gas measurements were performed at 446 min and 474 min from arterial blood samples taken via the carotid artery access line (diamond marker).

Figure 8

Mean absolute percentage errors calculated from the difference in measured lactate values performed between all implanted sensors and the blood gas analyzer across the first lactate and glucose challenges. Error bars describe the calculated standard errors for each sensor.

Figure 9

The (A) normalized peak lactate values, (B) response times, and (C) normalized average increase rates of subcutaneously implanted sensors during the first and second lactate challenges (n = 4 for each challenge). Error bars are described using standard errors.

Figure 10

A NO releasing central venous catheter (CVC) with mounted electrochemical lactate sensor after 10 h of placement within a femoral vein during the in vivo porcine study. The catheter orifice provides a measurement window for the active sensing region.