Reflex Sympathetic Dystrophy Clinical Trial
Official title:
Near-infrared Spectroscopic Measurement of Tissue Oxygen Saturation and the Vascular Occlusion Test in Complex Regional Pain Syndrome
Recent clinical investigations have suggested that the cause of abnormal pain in complex regional pain syndrome could be ischemia and inflammation, due to poor blood flow to deep tissues from microvascular pathology. This study aims to determine if a new technology called near infrared spectroscopy can measure this microvascular dysfunction. The study hypothesizes that significant differences can be measured in the microcirculation of patients with CRPS-I using near infrared spectroscopy and the vascular occlusion test.
The pathophysiology of CRPS-1 is unknown yet a considerable number of studies suggest that
the fundamental cause of abnormal pain is due to microvascular pathology of deep tissues.
Reduced blood flow to deep tissues such as muscle, nerve, and bone can lead to a combination
of inflammatory and neuropathic pain processes (Coderre TJ et al. 2010). Evidence to support
this model of microcirculatory dysfunction includes observations that skin capillary
oxygenation is decreased and skin lactate is increased in affected limbs of patients (total
of 11 patients in lactate study) (Birklein F et al. 2000, Manahan AP et al. 2007). It has
also been reported that patients with CRPS-I have abnormal vasodilatory responses after
sympathetically-mediated vasoconstriction (Dayan L et al. 2008) and decreased concentrations
of nitric oxide in the affected limb (Groeneweg JG et al. 2006).
Near-infrared spectroscopy (NIRS) is a non-invasive method of measuring tissue oxygenation
using the differential absorption properties of oxygenated and deoxygenated hemoglobin in
biological tissue (Creteur J 2008). Near-infrared light is only transmitted through small
vessels with diameter less than 1 mm (arterioles, venules and capillaries). Since NIRS is
limited to monitoring only small vessels, it can be used to assess oxygen balance in the
microcirculation of skeletal muscle (Creteur J 2008).
Premises Premise 1: Complex regional pain syndrome is associated with microcirculatory
dysfunction
After an injury to a patient's limb, it is hypothesized that the pressure exerted by that
swelling within a relatively confined anatomical space can occlude the capillaries of
adjacent tissues and cause a compartment syndrome-like injury. Coderre et al. (2010) have
theorized that the resulting microcirculatory dysfunction causes a persistent inflammatory
state which is then responsible for pain generation.
In an animal model of ischemia-reperfusion injury used to study CRPS-1, microscopy of muscle
and nerve tissue demonstrates microvascular evidence of a slow-flow/no-reflow phenomenon
(Coderre TJ et al. 2010). Existence of a slow-flow/no-reflow state causes persistent
inflammation in deep tissue. Animals subsequently develop hyperemia and edema, followed by
mechano-hyperalgesia, allodynia, and cold-allodynia lasting for at least 1 month (Coderre et
al. 2010). This clinical picture is similar to the clinical signs of those patients
afflicted with CRPS-1.
Premise 2: Vascular occlusion testing measures microcirculatory dysfunction NIRS measurement
of peripheral tissue oxygen saturation (StO2), combined with a reproducible
ischemia-reperfusion challenge to induce reactive hyperemia (vascular occlusion testing -
VOT), has been described as a valid and reliable method for assessing microcirculatory
dysfunction (De Backer et al. 2010). This involves a short period of forearm ischemia by
inflating a blood pressure cuff on the upper arm. The blood pressure cuff is then released
after approximately 3 minutes and this followed by reperfusion of the forearm. This
stimulates the release of endogenous nitric oxide (NO) from the microvascular endothelium
(Harel et al 2008). Measurement of this hyperemic response using NIRS has been demonstrated
to be a feasible non-invasive method of quantifying microcirculatory function. This
technique shares strong correlation with the gold-standard method of strain gauge
plethysmography (Harel et al. 2008).
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Observational Model: Case Control, Time Perspective: Prospective
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