Utility of Basal Laser Doppler Fluxmetry to Assess Resolution of Acute Vaso-Occlusive Episodes In Sickle Cell Disease

Abstract 4809

Currently in the field of sickle cell research there are no widely accepted and easily measured means of assessing resolution of a vaso-occlusive episode other than a patient's pain rating, amount of narcotic usage, or length of hospital stay. An easily applicable method of blood flow measurement would therefore be extremely useful. Laser-Doppler fluxmetry is a non-invasive technology that uses the frequency shift of laser light striking moving blood cells for the determination of blood flow. In previous studies in sickle cell patients using this technology, patient-discomforting provocations such as response to transient ischemia, heating, or cold stimulus have been required to show a difference between sickle cell patients and controls, due to large intra-patient variability seen in basal steady-state readings (Bachir D et al, Microvasc Res 1993). However, this variability may be due to long time intervals (2-3 weeks in previous studies) between basal measurements with no confirmation that measurements were repeated in precisely the same anatomic location. Spatial precision is important since blood flow can differ between areas only 1 cm apart (Rodgers GP et al, N Engl J Med 1984). No study, to our knowledge, has yet used successive laser Doppler measurements, basal or provocative, within a hospitalization for a vaso-occlusive episode in order to correlate with its resolution.

In this study, laser Doppler measurements (Periflux Model PF3 or PF5000, Perimed, Stockholm, Sweden) of the skin of the forehead and medial calf were assessed approximately every 8 hours from early in admission until hospital discharge in 8 subjects (6 females, 2 males) with SS or S ßthalassemia ranging in age from 10–35 (average 24, median 24) years enrolled in a Phase I clinical trial assessing intravenous immunoglobulin for treatment of acute vaso-occlusive episodes. Patients were normotensive, non-smoking, had no history of cardiovascular disease, no recent caffeine exposure, and no history of leg ulcers. The medial calf was chosen as a measurement site due to its clinical relevance in regard to leg ulcers and relative hairlessness. The forehead was chosen as a site due to report in the literature (in normal volunteers) of a relatively low (compared to other body sites) intra-individual coefficient of variation of 20% (Sundberg S, Scan J Clin Lab Invest 1984). Measurements over the length of the hospital stay were repeated in the precise same area (using a skin marker), with the subject in the supine position, using a 780 nm wavelength, 0.25 mm fiber separation, 1-cm diameter probe programmed to 34°C (to control for the inability to regulate room temperature in the standard inpatient units).

Averaging absolute perfusion or blood cell velocity measurements from all evaluable subjects at each time point (number of measurements evaluable at each time point differed according to the number of patients still hospitalized at that time point), there was no linear trend of improvement in blood flow over time in either body location. When averaging percentage (%) change between two consecutive measurements from all evaluable subjects at each time point, there was also no linear trend in blood flow improvement over time. However, when averaging within each subject the % change between consecutive measurements for the length of that subject's hospital stay, all patients showed a positive % change in blood flow in both body locations. In the medial calf, the average and median improvement was 20% and 11% (range 5–52%). In the forehead, the average and median improvement was 37% and 18% (range 1–194%).

We conclude that, despite efforts to mitigate possible circadian (Houben AJ et al, Scand J Clin Lab Invest 1994) and disease-related intra-individual patient variability, it is unlikely that basal laser Doppler flow measurements will be useful for real-time assessment of resolution of acute pain episodes. However, as all subjects showed an average % improvement in blood flow over the length of their hospital stay, basal laser Doppler measurements may still be useful as a research tool to compare the degree of blood flow improvement in a treatment versus control group for acute vaso-occlusive episodes. Its main potential advantage over pain ratings is greater objectivity; over narcotic usage greater independence from operator/provider bias; and over length of hospital stay greater resolution.