Fluid distribution and tissue resistance: response to intermittent pneumatic compression in people with and without primary lymphoedema

Author: J. Jane Phillips

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Phillips, J. Jane, 2022 Fluid distribution and tissue resistance: response to intermittent pneumatic compression in people with and without primary lymphoedema, Flinders University, College of Nursing and Health Sciences

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In primary lymphoedema, inherent drainage anomalies within the lymphatic system cause fluid accumulation in the dermis and subdermal tissues. Fluid accumulation progresses to fibrotic induration in both the dermis and subdermal tissues, which eventually become resistant to treatment, negatively impacting quality of life. However, no studies of primary lymphoedema have investigated dermal fluid accumulation, resulting in a lack of understanding of quantification and response to standard treatment. To better understand the dermis and subdermal tissues in primary lymphoedema, fluid distribution and tissue resistance in the leg and foot were explored in a cohort of 16 people with primary lymphoedema and compared to an age, gender and ethnicity matched group of 16 people with no lymphoedema. Objective clinical measures of lymphoedema—bioimpedance, percent water content, indurometry—provided subdermal information and circumferences provided a commonly used reference point. High frequency ultrasound (HFU) provided a measure of fluid specific to the dermis. The effect of a standardised dose of intermittent pneumatic compression on all measures was investigated and compared between groups.

The aims of this research were firstly to describe differences in these measures in the foot and leg between people with (PLO) and without (NLO) primary lymphoedema. The second aim was to understand the impact of compression on fluid distribution in primary lymphoedema compared to those with no lymphoedema. The final aim was to explore correlation among measures, to understand the relationships between them and identify possible proxy measures that might replace the need for the inaccessible and expensive HFU and provide simple cost-effective information to clinicians about dermal fluid status. Preparatory work for data collection involved establishing a reliable method of using HFU to measure dermal fluid using echogenicity measures.

In the observational study, significantly higher dermal fluid was observed in the foot in PLO compared to NLO. As well, local percent water content (PWC) and extracellular to intracellular fluid ratio (ECF/ICF) throughout the foot and leg were significantly elevated in PLO compared to NLO. Clinically, high dermal fluid measures in the feet of people with primary lymphoedema indicate the need for treatment to reduce fluid in the dermis of the foot before chronic pathological fibrotic changes occur.

An interventional study with the same group of people then compared the within group and between group changes in these outcome measures before and after one standardised dose of intermittent pneumatic compression (IPC). Dosage for IPC was informed by a systematic review. No significant change in dermal fluid occurred in response to IPC at any site in both groups, despite other fluid measures of ECF/ICF and PWC in PLO significantly decreasing after IPC, indicating that the effect of IPC on fluid distribution occurs deeper than the dermis. Lymphatic vessel anomalies in some forms of primary lymphoedema lead to delayed uptake of fluid from the dermis, which may account for the lack of change in the dermal fluid measures in this study. However, as no significant change was observed in dermal fluid in those with no lymphoedema, it appears that IPC does little to promote fluid uptake in the dermis. In addition, there was no response to IPC in the foot, demonstrated by all measures in both groups. Clinically, it appears that the foot requires an alternative and more effective strategy than IPC as applied, to manage the pathological changes commonly seen in the foot due to fluid accumulation in lymphoedema.

In the third investigation, moderately strong significant correlation was found between bioimpedance and percent water content in the leg. Tissue resistance was measured by the Indurometer, which indicated high tissue resistance by a low reading, and was the only measure to significantly correlate with two other measures. Firstly, there was moderate significant negative correlation between indurometry measures (IU) and PWC at the foot, indicating high tissue resistance (low IU) where percent water content was high. Secondly, a negative correlation was found between IU and the echogenic measures of dermal fluid at the posterior calf. This indicates lower tissue resistance (high IU) where there was low dermal fluid. As the Indurometer appears to be influenced by underlying tissue, and confidence intervals generated by bootstrapping were wide, further investigation is required prior to drawing any conclusions about correlation between the Indurometer and fluid measures.

This study demonstrates three original contributions to knowledge. High distal fluid accumulation was quantified by dermal and subdermal fluid measures in the foot and leg in people with primary lymphoedema compared to those with no lymphoedema, for the first time. This is consistent with lymphoscintigraphic descriptions of the distal fluid distribution in primary lymphoedema and supports treatment to the dermis and subdermal tissues in the foot in primary lymphoedema. The second original contribution was the observed lack of response to a single application of compression in the dermis at any site, based on the dosage applied. This raises important clinical questions about the effect on the initial lymphatics of less than an hour at 60 mmHg pressure as applied by IPC. Fluid uptake in the dermis is known to be influenced by variable pressure, which may not be optimally applied by IPC when supine. Furthermore, anomalous fluid uptake in the initial lymphatics in primary lymphoedema may have influenced the response to compression in PLO. The third original contribution was the lack of response to a single standardised dose of IPC in all measures in the foot. These findings warrant further investigation due to the high level of impact this may have on clinical practice. If IPC is ineffective in changing fluid accumulation in the foot, alternative evidenced treatment strategies are required and clinical practice adapted accordingly.

A focus for future research is to explore the dermal fluid response to other types of compression and other lymphoedema treatment modalities. In particular, investigation of modalities that move the skin, causing variable pressure in the dermis, may identify a treatment mode to reduce dermal fluid. Mapping the movement of fluid in the foot during IPC by ICG lymphography may assist in the development of optimal IPC dosage parameters to address fluid reduction in the foot, particularly in primary lymphoedema, in whom fluid uptake and pathways vary. Future dermal investigations of primary lymphoedema could benefit by additional baseline stratification by imaging or genetic abnormality. Determination of the baseline vessel anomaly or underlying fluid transport issues in future investigations may progress understanding of the dermal response to treatment in primary lymphoedema.

Keywords: Lymphoedema, primary lymphoedema, ultrasonography, intermittent pneumatic compression, skin, pressure

Subject: Health Sciences thesis

Thesis type: Doctor of Philosophy
Completed: 2022
School: College of Nursing and Health Sciences
Supervisor: Professor Sue Gordon