Simultaneous assessment of the synthesis rate and transcapillary escape rate of albumin in inflammation and surgery

Abstract

Background: Better knowledge of albumin kinetics is needed to define the indications for albumin use in clinical practice. This study involved two approaches: the synthesis rate and transcapillary escape rate of albumin were measured simultaneously at different levels of plasma albumin concentration in relation to acute inflammation and surgery; and two different tracers were compared to determine plasma volume and the transcapillary escape rate.

Methods: Healthy volunteers (n = 10), patients with acute inflammatory abdominal disease (n = 10), and patients undergoing elective pancreatic resection (n = 10) were studied. The albumin synthesis rate was measured by the incorporation of deuterium-labeled phenylalanine. Plasma volume and the transcapillary escape rate were assessed using ¹²³I-labeled and ¹²⁵I-labeled albumin.

Results: A 50 % elevated de-novo albumin synthesis rate was seen in patients with acute inflammation and marked hypoalbuminemia, while patients with marginal hypoalbuminemia before the start of surgery had a normal albumin synthesis rate. The transcapillary escape rate was elevated intraoperatively during the reconstructive phase of pancreatic surgery, when plasma albumin was decreased but stable. In acute inflammation with marked hypoalbuminemia, the transcapillary escape rate was no different from normal. ¹²³I-labeled and ¹²⁵I-labeled albumin were found exchangeable for plasma volume determinations, but could be used only in groups of patients for the transcapillary escape rate.

Conclusions: This observational study illustrates the limited information contained in albumin plasma concentrations to reflect albumin kinetics. On the contrary, single measurements of the synthesis rate and/or transcapillary escape rate of albumin obviously cannot explain the plasma level of albumin or the changes seen in plasma albumin concentration.

Trial registration: www.clinicaltrials.gov , study number NCT01686776 . Registered 13 September 2012.

Keywords: Albumin kinetics; Capillary leakage; Hypoalbuminemia.

Fig. 1

Plasma albumin concentration over time. a Healthy volunteers (n = 9). b Surgical patients with acute inflammation (n = 10). c Patients undergoing pancreatic resection (n = 9). Green area, albumin synthesis measurements; gray area, measurement of the TER and PV. x axes are not linear and are different in the three panels. In c T ₁ denotes the start of the reconstruction phase during surgery, 277 ± 94 min after the beginning of the surgical procedure. Concentrations of all individual patients are given in the three panels and the median values are indicated (red line). On a group level, plasma albumin concentration was stable in healthy subjects and patients with acute inflammation, while plasma albumin concentration decreased until the start of the reconstruction phase during pancreatic surgery. P-albumin plasma albumin, Whipple pancreatic surgery

Fig. 2

Fractional synthesis rate (FSR) and absolute synthesis rate (ASR) of albumin in healthy volunteers (n = 10, blue), in surgical patients with acute inflammation (n = 10, red), and in patients undergoing pancreatic resection (n = 9, green) as measured by incorporation of d5-phenylalanine into protein. Median values indicated by black lines. Patients with acute inflammation were different from the two other groups for both aspects of the synthesis rate (P < 0.001). Whipple pancreatic surgery

Fig. 3

Transcapillary escape rate of albumin (TER) in healthy volunteers (n = 9, blue), in surgical patients with acute inflammation (n = 10, red), and in patients undergoing pancreatic resection (n = 9, green) as measured by ¹²³I-albumin and ¹²⁵I-albumin, respectively. Median values indicated by black lines. The TER is different during pancreatic surgery as compared with controls for both ¹²³I-albumin and ¹²⁵I-albumin. HSA human serum albumin, Whipple pancreatic surgery

Fig. 4

Plasma volume (PV) in healthy volunteers (n = 9, blue), in surgical patients with acute inflammation (n = 10, red), and in patients undergoing pancreatic resection (n = 9, green) as measured by ¹²³I-albumin and ¹²⁵I-albumin, respectively. To make groups more comparable the measured PVs are related to the anthropometrically calculated PVs [14]. Median values indicated by black lines. No difference in PV between the three groups was detected. HSA human serum albumin, Whipple pancreatic surgery

Fig. 5

Bland–Altman plots demonstrating agreement between measurements of the transcapillary escape rate (TER) and plasma volume (PV) as measured by ¹²³I-albumin and ¹²⁵I-albumin, respectively, in healthy volunteers (n = 9, blue), in surgical patients with acute inflammation (n = 10, red), and in patients undergoing pancreatic resection (n = 9, green. Limits of agreement given as the mean difference ± 2.045 SD (n = 28, hatched lines) and the line of identity (solid line) are shown