Evaluate the Nephrotoxicity by 6% Hydroxyethyl Starch 130/0.4 in Old Patients During Orthopaedic Surgery
Condition: Total Fluid Volume Increased
Study type: Interventional

Summary: 
      Hydroxyethyl starch (HES) is commonly used as plasma expander during surgery but may be
      nephrotoxic as seen in studies in patients with sepsis. The investigators hypothesized that
      the possible nephrotoxicity of 6% HES 130/0.4 could be revealed by measurements of urinary
      and plasma neutrophil gelatinase-associated lipocalin and interleukin-18 (IL-18) in old
      patients with normal renal function during orthopaedic surgery.
    

Detailed description: 
      Hydroxyethyl starch (HES) is widely used as volume expander to maintain circulation in
      patients during surgery, trauma, and in critical disease, where a rapid and sustained volume
      expansion is the goal. However, acute kidney injury (AKI) is sometimes a complication in
      these patients and HES might be a contributing factor. Acute kidney injury is often diagnosed
      using a sudden rise in plasma creatinine (p-crea) or an abrupt decrease in urine output.
      P-crea depends on sex, nutrition, medication,muscle mass, and age and it increases 24 to 48 h
      after renal injury, so the diagnosis of AKI is delayed when using p-crea alone as an
      indicator for renal damage. New technology allows for earlier diagnosis of AKI using
      measurements of biomarkers in urine. Neutrophil gelatinase-associated lipocalin (NGAL) is a
      small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules,
      and thus low concentrations of NGAL can be measured in the blood and urine. Approximately 6 h
      after a renal injury, NGAL increases rapidly due to an up-regulated expression and secretion
      in the epithelial cells of the thick ascending limb of Henle's loop, the distal tubules, and
      the collecting ducts. Thus, NGAL can be used as a marker of renal damage. However, infections
      and malignancies can give falsely increased levels.

      Interleukin-18 (IL-18) is mainly created from proximal kidney tubules which is a
      proinflammatory factor that can be detected in earlier urine of AKI animal models. There is
      significant rise in IL-18 levels in urine of AKI confirmed cases(no chronic kidney disease,
      no urinary tract infections, no prerenal factors), specificity and susceptibility is 90%. As
      a result, IL-18 can be selected as a biomarker.

      Intravenously administrated HES is excreted in urine but is also partly accumulated in the
      tissues. Studies in animals and humans showed that HES molecules were accumulated in the
      proximal tubule cells with subsequent vacuolization and swelling-a condition known as osmotic
      nephrosis. However, recent studies, primarily conducted in patients with sepsis, found
      impaired renal function even when using tetrastarch. In contrast, perioperative studies found
      no evidence of AKI after infusion of HES. The investigators hypothesized that 6% HES 130/0.4
      had a nephrotoxic effect, which could be revealed by measurements of urinary and plasma NGAL
      and IL-18; that 6% HES 130/0.4 influenced kidney function differently than
      crystalloids(lactated Ringer's solution) due to the different pharmacokinetic properties of
      colloids compared with that of crystalloids.
    

Intervention name(s): Hydroxyethyl Starch; Lactate Ringers
Intervention type(s): Drug; Drug
Intervention description(s): 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery; Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery
Other intervention name(s): HES; LR
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)