Pros and cons of tetrastarch solution for critically ill patients

Abstract

Proper fluid management is crucial for the management of critically ill patients. However, there is a continuing debate about the choice of the fluid, i.e., crystalloid vs. colloid. Colloid solution is theoretically advantageous to the crystalloid because of larger volume effect and less interstitial fluid accumulation, and hydroxyethyl starch (HES) is most frequently used for perioperative setting. Nevertheless, application of HES solution is relatively limited due to its side effects including renal toxicity and coagulopathy. Since prolonged presence of large HES molecule is responsible for these side effects, rapidly degradable HES solution with low degree of substitution (tetrastarch) supposedly has less potential for negative effects. Thus, tetrastarch may be more frequently used in the ICU setting. However, several large-scale randomized trials reported that administration of tetrastarch solution to the patients with severe sepsis has negative effects on mortality and renal function. These results triggered further debate and regulatory responses around the world. This narrative review intended to describe the currently available evidence about the advantages and disadvantages of tetrastarch in the ICU setting.

Effects of 6% tetrastarch or lactated Ringer's solution on blood coagulation in hemorrhaged dogs

“…Despite a transient increase in aPTT induced by TS, the decrease in MCF in‐TEM of similar magnitude and duration (4 hours) induced by VR with LRS and TS supports the hypothesis that the hypocoagulable effect of TS was a dilutional effect, and suggests that the intrinsic coagulation pathway (factor VIII) was impaired to the same degree by both fluids. This finding is in agreement with the concept that HES solutions with smaller molecular weight and molar substitution, such as third generation TS, cause less interference with coagulation than HES solutions of larger molecular weight …”

“…Activated partial thromboplastin time transiently increased from controls 4 hours after TS administration ( P = 0.045), suggesting that TS caused an impairment in the intrinsic coagulation pathway. Hydroxyethyl starch solutions may interfere with factor VIII and inhibit the intrinsic coagulation pathway by 2 mechanisms: (1) direct decrease of activated factor VIII beyond a dilutional effect, and (2) direct binding and inactivation of factor VIII . Although a decrease in factor VIII activity may be observed with HES solutions of larger molecular weight, large doses of TS administered to dogs (40 mL/kg) and humans (50‐70 mL/kg) did not decrease factor VIII concentrations.…”

“…In a previous study of dogs anesthetized using a fixed end‐tidal isoflurane concentration (1.3 times the minimum alveolar concentration), removal of 30% of blood volume resulted in hypotension (MAP < 60 mm Hg) in half of the studied population (4/8 dogs) . Because of concerns with renal injury in animals that would receive a fluid that might predispose to renal damage (TS), the end‐tidal isoflurane concentration was adjusted to provide immobility and to maintain MAP within ranges that usually are considered acceptable during anesthesia (MAP between 60 and 70 mm Hg) …”

“…Use of hydroxyethyl starch (HES) solutions is controversial in human medicine because the use of these fluids may be associated not only with acute kidney injury but also with impaired coagulation . The coagulopathy associated with HES solutions may involve several mechanisms, including: (1) inhibition of the formation of the fibrin network because of binding and inactivation of factor VIII and von Willebrand's factor (vWF); (2) inhibition of blood clot formation by inhibition of glycoproteins GP IIb/IIIa located on the surface of activated platelets; (3) inhibition of the binding of GP IIb/IIIa platelet receptors to vWf and fibrinogen; and (4) acceleration of fibrin degradation …”

Fluid Therapy and Management

“…Ayrıca, son çalışma ve yayınlar böbrek fonksiyonlarında klor etkisi üzerine dikkat çekmektedir. Dolayısıyla NaCl bazlı HES preparatları açısından bu noktaya da dikkat edilmelidir (34) . Akut Böbrek Hasarını (AKI) önlemede riskli hastaları olabildiğince erken tanımak çok önemlidir.…”