Background:
Chemotherapy-induced peripheral neuropathy (CIPN) as common side effect not only severely restricts quality of life but also therapy options to first-line therapies in cancer patients. Compression therapy has been postulated as beneficial through reduction of microvascular neuronal perfusion and included in current guidelines. Existing data to substantiate this assertion are contradictory. We sought to resolve the physiological basics and potential vascular components in order to substantiate the development of a potential novel CIPN-treatment.
Methods:
In 20 healthy controls (50% male; age 24.5 ± 4.3 years) and 12 patients with peripheral arterial disease (PAD, 75% male, age: 68 ± 9, 42% longstanding diabetics, serving as positive controls for endothelial dysfunction) as well as 12 chemotherapy (CTX) patients local tissue oxygenation (haem (h) as in haemoglobin and myoglobin) as well as endothelial function were measured with quantitative time resolved near infra-red spectroscopy (NIRS) and thermography on hands in response to dynamic static compression (DSC) with commercially available compression products and patented palmar or plantar pads or 2 undersized surgical gloves (SG) for up to 90 minutes under standardised and controlled conditions. Friedman test with a trend (p<0.1) was required before individual analyses, Bonferroni-Holm correction was used for multiple comparisons.
Results:
Significant reduction in skin temperature of - 2°C to - 6° C were achieved with compression products (both, SG and DSC) all 3 groups (p<0.01 each combination). In controls, SG time-dependently increased relative local tissue oxygenation saturation (StO2: 0.9±1.4 to 5.2±4.9%, p<0.05) and oxygen supply (O2h: 0.8±6.7 to 3.6±12.2 µM/s, p<0.05) and reduced metabolism (dh: -4.8±9.0%, p<0.05) over 30 minutes, subsequently returning to baseline. In contrast (p<0.05 each), DSC in controls instantly reduced metabolic oxygen demand of the intervened hand (dh: -4.6±2.4%) that remained on a low level only influenced by opening of the capillary bed after 5 to 30 minutes (th: +5.6±7.5%, p<0.01) with constant increase of local tissue oxygenation (StO2: +11.2±7.0%, p<0.001) for the entire 90 minutes driven by increased oxygen supply (O2h: +11.7±7.3 µM/s, p<0.001) and microvascular perfusion (th: 7.6±8.7%, p<0.005) for the entire compression period. This effect is reversible immediately after the DSC is removed. Only through achieving uniform elevated pressure with DSC, optimised oxygen delivery to oxygen utilisation continued over 20min after the actual compression period (p<0.001). In PAD and in CTX after therapy, magnitude of the increase in StO2 was significantly lower than in controls (p<0.05 each), whereas reduction of dh during DSC was comparable, as evidence of the partial vascular component of the effect of compression therapy.
Conclusion:
Contrary to the previously held view, as evidenced in our studies, compression of hands and feet does not lead to a reduction in microvascular perfusion, but rather causes a vascular-related improvement of oxygen delivery and diffusion, and thus, in local tissue oxygenation. Rather, reduction of local metabolic oxygen demand is responsible for reduction of local tissue temperature. Mechanisms of action are shown here for the first time and the physiological laws that can be derived from them must be taken into account if compression therapy for primary and secondary prevention of CIPN is to be successful.