Research Article: Interstitial Fluid Colloid Osmotic Pressure in Healthy Children

Date Published: April 8, 2015

Publisher: Public Library of Science

Author(s): Hans Jørgen Timm Guthe, Marianne Indrebø, Torbjørn Nedrebø, Gunnar Norgård, Helge Wiig, Ansgar Berg, Yoshihiro Fukumoto.


The colloid osmotic pressure (COP) of plasma and interstitial fluid play important roles in transvascular fluid exchange. COP values for monitoring fluid balance in healthy and sick children have not been established. This study set out to determine reference values of COP in healthy children.

COP in plasma and interstitial fluid harvested from nylon wicks was measured in 99 healthy children from 2 to 10 years of age. Nylon wicks were implanted subcutaneously in arm and leg while patients were sedated and intubated during a minor surgical procedure. COP was analyzed in a colloid osmometer designed for small fluid samples.

The mean plasma COP in all children was 25.6 ± 3.3 mmHg. Arbitrary division of children in four different age groups, showed no significant difference in plasma or interstitial fluid COP values for patients less than 8 years, whereas patients of 8-10 years had significant higher COP both in plasma and interstitial fluid. There were no gender difference or correlation between COP in interstitial fluid sampled from arm and leg and no significant effect on interstitial COP of gravity. Prolonged implantation time did not affect interstitial COP.

Plasma and interstitial COP in healthy children are comparable to adults and COP seems to increase with age in children. Knowledge of the interaction between colloid osmotic forces can be helpful in diseases associated with fluid imbalance and may be crucial in deciding different fluid treatment options. NCT01044641

Partial Text

Maintenance of body fluid homeostasis requires a delicate balance between the hydrostatic and colloid osmotic pressure (COP) acting across the intravascular and interstitial compartments. According to the classical Starling hypothesis, the net fluid shift across the capillary membrane is based on the interaction between two opposing forces: the difference in hydrostatic pressures and COP on either side of the membrane separating the capillary and the interstitial fluid (IF) spaces [1]. Studies of these parameters under various conditions with fluid retention (e.g. nephrotic syndrome [2], premenstrual syndrome [3], normal pregnancy [4] and cardiopulmonary disease [5]) in humans have had great significance for understanding the pathophysiology of these disorders, and have in some cases been important in the choice of fluid treatment [5]. The normal values for colloid osmotic and hydrostatic pressures in the resting state of healthy children have not been established, largely because of methodological difficulties in measurements of each of the parameters. In the case of interstitial colloid osmotic pressure (COPi), this is likely due to lack of generally accepted methods for isolating IF. What is clear, however, is that plasma colloid osmotic pressure (COPp) increases during the first months after birth, reaching at one year of age, values comparable to those reported in adult subjects [6]. Furthermore, decreased COPp in disease states, like congenital analbuminemia and during surgery for congenital cardiac malformations, is associated with compromised pulmonary function and tissue edema [7, 8]. A commonly accepted method for IF sampling and thus COPi determination is implantation of wicks [9, 10] within the proximity of the heart assuming that this position represents the average capillary pressure [11]. Gravity is thought to influence the transcapillary pressures measured below the heart level with decreased interstitial COP from an increased hydrostatic pressure gradient [11]. Harvesting IF has traditionally been managed by extraction of fluid from subcutaneously implanted nylon wicks [9]. Although evaluation studies have shown that an implantation time of 60 minutes is appropriate in adults, this supposition is not necessarily true for the pediatric population. Establishing normal values of COPi in healthy children can be vital for proper fluid therapy in critically ill children. The aim of this study was primarily to evaluate the relationship between COPp and COPi in healthy children of different age. Secondly, we wanted to test if gravity would induce a difference in COPi obtained from arm and leg and thirdly to evaluate implantation times of wicks of 60 and 90 minutes.

The study was designed as a non-blinded, sequential, descriptive study, taking place between 05. January 2007 and 22. January 2012. Patient enrolment began before study trial was registered ( Identifier: NCT01044641, due to the authors not being aware of the need for registration when the study was initiated. The authors confirm that all ongoing and related trials for this intervention are registered. The protocol was approved 29. September 2006 by the local ethics committee (Regional Committee for Medical and Health Research Ethics, Western Norway) and conducted at the outpatient clinic, Department of Ear-Nose-Throat, Haukeland University Hospital. Patients were also recruited from the Department of Ear-Nose-Throat, Akershus University Hospital from May 2010 to June 2010 to increase number of participants. Ethics approval was not necessary from Akershus University Hospital because of the existing approval from the Regional Committee for Medical and Health Research Ethics, Western Norway. For CONSORT checklist, Ethical Confirmation and Trial Protocol in Norwegian and English; see S1 CONSORT Checklist, S1 Ethics approval, S1 Protocol and S2 Protocol. The time period for patient recruitment was prolonged after approval from the local ethics committee, due to delayed enrolment of patients.

Patients and outcome: A total of 99 children (45 girls and 54
boys), were included in the study (Fig 1), and 92 (93%) had weights within ± 2 SD according to Norwegian growth charts (S1 Fig). Eleven participants (mean age 4 years 8 months) had blood loss greater than 10% of estimated CBV (Fig 2). Nineteen percent of wicks were discarded due too blood staining of wick or insufficient sample size (Fig 2). In average, 5 l of interstitial fluid was harvested from each wick. Preoperative hemoglobin (Hb) measured in 83 patients (84%) less than eight days before surgery averaged 12.5 g/dl (range 10.5–15.0). Serum Albumin was measured before surgery in 32 patients (32%) with mean albumin of 44 g/l (range 38–52) and no statistical difference was found between the different age groups. There were no immediate (before discharge) or long time (phone interview 7 days after the procedure) complications due to wick implantation or blood sampling.

In this study, COPp and COPi in healthy children were close to what has been reported for healthy adults [21], but both COPp and COPi were significantly higher at 8–10 years than in younger children. Whether COPi was obtained at or below heart level, or after 60 or 90 minutes, did not influence the results. There were no complications to using nylon wicks, suggesting that this method is safe for harvesting IF in anesthetized children. Furthermore, the method also gave sufficient volumes of IF to allow COP measurements. In rats, the optimal time needed for fluid and protein transport into the wick with a minimum of inflammation is between 30 and 120 minutes [19]. As suggested for healthy adults [14, 15], we found that 60 minutes was sufficient implantation time for collection of IF.