Subcutaneous tissue is a promising alternative site for monitoring stress in vivo

Blood pH (acidity) is a useful indicator of the state of a living system. As such, it can be valuable in determining the physiologic status of critically ill patients. It is typically measured on demand—along with so-called blood gases—by drawing blood samples and having them tested in the laboratory. The need for very frequent or continuous monitoring of these parameters has spurred the development of many intravascular optical fiber sensors.¹ Reliability of measurements under clinical conditions (3–5h in the operating room and up to two to three days in intensive care units) is a major challenge, however, and no sensor developed to date has been fully satisfactory.² Moreover, these devices are expensive. The only continuous monitor currently in use in open-heart operations is an extravascular system for extracorporeal (outside the body) blood circulation (CDI Blood Parameter Monitoring System 500, Terumo).

Microdialysis offers an alternative that is less invasive than intravascular techniques. It also has potential for cases where blood loss from diagnostic samples may pose serious risks, for example, with hospitalized infants or intensive care patients.³ In microdialysis, a semipermeable hollow-fiber dialysis membrane is introduced into tissue, and intracellular (interstitial) fluid is extracted via a catheter. The fluid emerging from the catheter—the perfusate—contains information about the concentration of the diffusing molecules in the interstitial fluid. Fluid samples are generally collected for analysis to be carried out off-line using external instrumentation. On-line miniaturized sensors have also recently been developed.

Figure 1. Schematic illustration of a fluidic system for microdialysis measurements. The expanded insets show the connection to the microdialysis catheter as well as between the optical fibers and the pH-sensing capillary.

The interstitial fluid drawn from the patient flows through a microfluidic circuit formed by the microdialysis catheter in series with a glass capillary. A pH indicator, phenol red, is chemically immobilized on the internal wall of the capillary (see Figure 1).⁴ A so-called carrier solution is supplied to the catheter from a reservoir by a peristaltic pump at a flow rate of 2μl/min. Absorption alterations in the sensing layer, which depend on the pH of the flowing carrier solution, are measured using two optical fibers connected to a home-made optoelectronic interrogation unit. An accuracy of 0.05pH in the range 6–8 was obtained along with a response time on the order of a minute.

An animal model was developed to create a situation of stress, based on drawing more than 50% of the blood in a pig and subsequent reinjection after 1h.⁵ The microdialysis catheter is introduced in the abdomen of the pig. Blood pH values are measured roughly every 30min with a blood gas analyzer. A glass microelectrode inserted close to the microdialysis catheter is used as reference. As the blood is drawn, a decrease in pH is observed in the blood and the fatty tissue, which on reinjection both also reflect the recovery of the animal with a return to a more healthy state (see Figure 2). The discrepancy of 0.1–0.2pH between the glass microelectrode (characterized by a resolution of 0.1pH) and the optical sensor is due to the low resolution of the electrode (0.1pH). In addition, the microelectrode samples the pH at a well-localized point, whereas optically measured pH is the average value taken over a region the length of the microdialysis catheter (35mm).

Figure 2. Changes in blood pH detected by the optical sensor (red tracing) and the glass electrode under the tissue (blue tracing) during drawing and subsequent reinjection of 50% of blood. Dark red dots indicate the value of arterial blood pH. The vertical black lines indicate the start and end of blood drawing, and the start of blood reinfusion.

The results obtained are very encouraging. Fatty tissue appears to be a reliable alternative site for in vivo continuous monitoring of stress conditions. Further in vivo measurements on animals are in progress—with the addition of optical sensors for blood gases—and the first tests involving human volunteers have been scheduled.

This research study was supported by the European Community within the framework of the four-year EU-funded Information Society Technologies priority project CLINICIP (Closed Loop INsulin Infusion for Critically Ill Patients).