Transcapillary fluid balance in children. Methodology and new clinical studies. To the interstitial space - and back again

Objective: The capillaries represent a semipermeable barrier between the blood and the interstitium, where there is a continuous exchange of fluid and solutes. Numerous factors affect the tight regulation of this movement across the microvasculature, with transmural pressure gradient being a key element governed according to the Starling equation. Colloid osmotic pressures, acting on both sides of the capillaries, are one class of forces defining the movement of fluid between the capillaries and interstitial spaces, and these are influenced by age, maturation, health, and disease. There is limited knowledge on the capillary-interstitial exchange in children that favours extravasation of fluid. Our understanding of paediatric fluid balance is to a certain extent based on practical experience, observation, and extrapolation of data obtained in the adult population, rather than on precepts or theory. The studies included in this thesis work were aimed at evaluating a method for sampling subcutaneous interstitial fluid, studying the interstitial and plasma colloid osmotic pressure in the paediatric population, and at gaining a better understanding of local inflammation during asphyxia, in paediatric subjects. Methods and Results: In healthy adults, the colloid osmotic pressure of subcutaneous fluid sampled by implanted nylon wicks was similar to that reported in previous studies using other sampling methods. Comparing plasma and interstitial fluid using high performance liquid chromatography excluded the possibility of contamination with haemoglobin and other macromolecules in wicks, and indicates that this sampling method is only mildly traumatic. Colloid osmotic pressures obtained from saline-soaked wicks implanted for different time periods indicate that an optimal implantation time is between 75-90 minutes. There was no significant difference in colloid osmotic pressures obtained by dry or wet nylon wicks. Interstitial colloid osmotic pressure also did not differ for implantation times of 60 or 90 minutes in children. Sixty minutes of topical application of anaesthetic cream before insertion of wicks reduced the pain experience, and did not influence colloid osmotic pressure. This result argues that wicks could likely be used reasonably in the paediatric population. Boys and girls between 2 and 10 years old had colloid osmotic pressure in plasma similar to that measured in adults, showing increasing age-specific values for interstitial and plasma colloid osmotic pressure. The altered colloid osmotic pressure gradient that occurs during the ages of 2 to 7 years may facilitate fluid transport into the capillaries and reduce lymphatic absorption for the purpose of preserving homeostasis. The colloid osmotic pressure gradient for asphyxiated neonates was unaltered throughout therapeutic hypothermia treatment, showing decreased interstitial and plasma colloid osmotic pressure compared to healthy-term neonates. Cytokine levels during therapeutic hypothermia, as measured by magnetic bead immunoassay, were elevated for IL-1α in tissue and reduced in serum for IL- 1RA, IL-6, IL-8, and IL-10, suggesting a balanced inflammatory stimulus. This is underscored by a decreased white blood cell count, which is known to be beneficial for recovery after brain injury. Conclusions: The wick method is a feasible method for sampling native interstitial fluid in adults and is now demonstrated to be applicable also in children, if performed with topical anaesthesia. Implantation times of 60-90 minutes are sufficient for sampling fluid in both adults and children to avoid cellular inflammation due to implantation trauma. The optimal harvesting time within this time frame is uncertain. Asphyxiated neonates have lowered interstitial and plasma colloid osmotic pressure and reduced colloid osmotic pressure gradient, which may be a normal physiological and beneficial response to therapeutic hypothermia treatment, combined with an overall immunosuppressive effect. The finding of comparable colloid osmotic pressures in children between 2 and 10 years of age and in adults, and for infants over 2 months of age, suggests a change occurs as part of the circulatory transformations that take place after birth