Effect of topical anaesthetics on interstitial colloid osmotic pressure in human subcutaneous tissue sampled by wick technique

Abstract

Objectives: To measure colloid osmotic pressure in interstitial fluid (COP(i)) from human subcutaneous tissue with the modified wick technique in order to determine influence of topical application of anaesthetics, dry vs. wet wick and implantation time on COP(i).

Material and methods: In 50 healthy volunteers interstitial fluid (IF) was collected by subcutaneous implantation of multi-filamentous nylon wicks. Study subjects were allocated to two groups; one for comparing COP(i) obtained from dry and saline soaked wicks, and one for comparing COP(i) from unanaesthetized skin, and skin after application of a eutectic mixture of local anaesthetic (EMLA®, Astra Zeneca) cream. IF was sampled from the skin of the shoulders, and implantation time was 30, 60, 75, 90 and 120 min. Colloid osmotic pressure was measured with a colloid osmometer. Pain assessment during the procedure was compared for EMLA cream and no topical anaesthesia using a visual analogue scale (VAS) in a subgroup of 10 subjects.

Results: There were no significant differences between COP(i) obtained from dry compared to wet wicks, except that the values after 75 and 90 min. were somewhat higher for the dry wicks. Topical anaesthesia with EMLA cream did not affect COP(i) values. COP(i) decreased from 30 to 75 min. of implantation (23.2 ± 4.4 mmHg to 19.6 ± 2.9 mmHg, p = 0.008) and subsequently tended to increase until 120 min. EMLA cream resulted in significant lower VAS score for the procedure.

Conclusion: COP(i) from subcutaneous tissue was easily obtained and fluid harvesting was well tolerated when topical anaesthetic was used. The difference in COP(i) assessed by dry and wet wicks between 75 min. and 90 min. of implantation was in accordance with previous reports. The use of topical analgesia did not influence COP(i) and topical analgesia may make the wick technique more acceptable for subjects who dislike technical procedures, including children.

Trial registration: ClinicalTrials.gov NCT01044979.

Figure 1. Colloid osmotic pressure and implantation time.

Colloid osmotic pressure in interstitial fluid collected from wicks after various times of implantation. Significant difference (p<0.05) between dry (•) and wet (▪) wicks at 30 min. are indicated with () and between dry wicks from 30 to 75 min. with ().

Figure 2. Topical anaesthesia and colloid osmotic pressure.

Colloid osmotic pressure in interstitial fluid collected from wet wicks inserted without (•) or after topical anaesthesia with EMLA (▴) plotted against duration of insertion. Mean COP_i was 21.0 mmHg in the group without and 20.6 mmHg in the group with EMLA. No significant differences were found between the groups.

Figure 3. Distribution of macromolecules in interstitial fluid.

High resolution size exclusion chromatography of plasma (black line) and interstitial fluid derived from: A; dry (red line) or wet (blue line) wicks, B; wet wicks with (red line) or without (blue line) topical anaesthetics. Wicks were collected after 60 min. of implantation. Ordinate: Absorption units at UV 210 normalized to the highest peak (HSA). Retention time for human serum albumin (HSA), IgG and alpha 2 macroglobulin (α2M) standards indicated. A small haemoglobin peak between 11 and 12 min. retention was usually seen in interstitial fluid.